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The Database: New 06/27/2006 05:11 PM

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Nomenclature Committee of the International Union of and Molecular Biology (NC-IUBMB) Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC- IUBMB by Keith Tipton, Sinéad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were put on the web by Gerry Moss. Comments and suggestions on these draft entries should be sent to Professor K.F. Tipton and Dr S. Boyce (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland) by 20 May 2006, after which, the entries will be made official and will be incorporated into the main enzyme list. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

Many thanks to those of you who have submitted details of new enzymes or updates to existing enzymes.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.

Contents

*EC 1.1.1.262 4-hydroxythreonine-4-phosphate dehydrogenase EC 1.1.1.289 EC 1.1.1.290 4-phosphoerythronate dehydogenase EC 1.1.99.19 transferred *EC 1.2.1.10 acetaldehyde dehydrogenase (acetylating) EC 1.2.1.71 succinylglutamate-semialdehyde dehydrogenase EC 1.2.1.72 erythrose-4-phosphate dehydrogenase EC 1.2.99.1 transferred *EC 1.3.99.19 quinoline-4-carboxylate 2- *EC 1.4.3.5 pyridoxal 5′-phosphate synthase *EC 1.4.4.2 (decarboxylating) EC 1.7.1.13 queuine synthase *EC 1.8.1.4 dihydrolipoyl dehydrogenase *EC 1.11.1.14 EC 1.11.1.16 *EC 1.13.11.11 tryptophan 2,3-dioxygenase *EC 1.13.11.19 EC 1.13.11.42 deleted EC 1.13.11.52 indoleamine 2,3-dioxygenase EC 1.13.11.53 acireductone dioxygenase (Ni2+-requiring) EC 1.13.11.54 acireductone dioxygenase [iron(II)-requiring] EC 1.13.11.55 /reductase EC 1.13.12.14 -a oxygenase EC 1.14.13.65 deleted EC 1.14.13.101 senecionine N-oxygenase *EC 1.14.99.3 oxygenase EC 1.17.99.4 /thymine dehydrogenase *EC 2.1.2.10 *EC 2.3.1.11 thioethanolamine S- *EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase *EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase *EC 2.3.1.41 β-ketoacyl-acyl-carrier-protein synthase I *EC 2.3.1.109 arginine N-succinyltransferase EC 2.3.1.177 EC 2.3.1.178 diaminobutyrate acetyltransferase EC 2.3.1.179 β-ketoacyl-acyl-carrier-protein synthase II EC 2.3.1.180 β-ketoacyl-acyl-carrier-protein synthase III EC 2.3.1.181 lipoyl(octanoyl) *EC 2.4.1.195 N-hydroxythioamide S-β-glucosyltransferase

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EC 2.4.1.243 6G-fructosyltransferase EC 2.4.1.244 N-acetyl-β-glucosaminyl-glycoprotein 4-β-N-acetylgalactosaminyltransferase *EC 2.6.1.52 phosphoserine transaminase *EC 2.6.1.76 diaminobutyrate—2-oxoglutarate transaminase EC 2.6.1.81 succinylornithine transaminase EC 2.6.99.2 pyridoxine 5′-phosphate synthase *EC 2.7.1.151 inositol-polyphosphate multikinase EC 2.7.1.158 inositol-pentakisphosphate 2-kinase EC 2.7.1.159 inositol-1,3,4-trisphosphate 5/6-kinase EC 2.7.4.22 UMP kinase EC 2.7.7.63 lipoate—protein *EC 2.8.1.6 EC 2.8.1.8 EC 3.1.3.76 lipid-phosphate phosphatase EC 3.1.13.5 ribonuclease D *EC 3.1.26.3 ribonuclease III *EC 3.2.1.81 β- *EC 3.2.1.83 κ-carrageenase EC 3.2.1.155 xyloglucan-specific exo-β-1,4-glucanase EC 3.2.1.157 ι-carrageenase EC 3.2.1.158 α-agarase EC 3.2.1.159 α-neoagaro-oligosaccharide EC 3.2.1.161 β-apiosyl-β-glucosidase EC 3.3.2.3 transferred *EC 3.3.2.6 leukotriene-A4 hydrolase *EC 3.3.2.7 hepoxilin- EC 3.3.2.9 microsomal epoxide hydrolase EC 3.3.2.10 soluble epoxide hydrolase EC 3.3.2.11 cholesterol-5,6-oxide hydrolase EC 3.4.21.87 transferred EC 3.4.23.49 omptin EC 3.5.1.94 γ-glutamyl-γ-aminobutyrate hydrolase EC 3.5.1.95 N-malonylurea hydrolase EC 3.5.1.96 succinylglutamate desuccinylase *EC 3.5.2.1 EC 3.5.3.23 N-succinylarginine dihydrolase *EC 3.6.3.5 Zn2+-exporting ATPase *EC 3.6.3.44 xenobiotic-transporting ATPase EC 3.6.3.45 deleted *EC 4.1.1.21 phosphoribosylaminoimidazole carboxylase EC 4.1.1.86 diaminobutyrate decarboxylase *EC 4.1.2.8 indole-3-glycerol-phosphate EC 4.1.3.39 4-hydroxy-2-oxovalerate aldolase *EC 4.2.1.60 3-hydroxydecanoyl-[acyl-carrier-protein] EC 4.2.1.108 *EC 4.2.3.9 EC 4.2.3.22 EC 4.2.3.23 germacrene-A synthase EC 4.2.3.24 amorpha-4,11-diene synthase EC 4.2.3.25 S-linalool synthase EC 4.2.3.26 R-linalool synthase EC 4.4.1.24 sulfolactate sulfo-lyase EC 4.4.1.25 L-cysteate sulfo-lyase EC 5.3.3.14 trans-2-decenoyl-[acyl-carrier protein] EC 5.4.99.18 5-(carboxyamino)imidazole ribonucleotide mutase *EC 6.3.2.6 phosphoribosylaminoimidazolesuccinocarboxamide synthase *EC 6.3.2.27 EC 6.3.4.18 5-(carboxyamino)imidazole ribonucleotide synthase

*EC 1.1.1.262 Common name: 4-hydroxythreonine-4-phosphate dehydrogenase Reaction: 4-(phosphonooxy)-L-threonine + NAD+ = (2S)-2-amino-3-oxo-4-phosphonooxybutanoate + NADH + H+ For diagram of pyridoxal biosynthesis, click here Other name(s): NAD+-dependent threonine 4-phosphate dehydrogenase; L-threonine 4-phosphate dehydrogenase; http://www.enzyme-database.org/newenz.php?sp=off Page 2 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

4-(phosphohydroxy)-L-threonine dehydrogenase; PdxA Systematic name: 4-(phosphonooxy)-L-threonine:NAD+ oxidoreductase Comments: The of the reaction undergoes decarboxylation to give 3-amino-2-oxopropyl phosphate. In Escherichia coli, the coenzyme pyridoxal 5′-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4- phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4- hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5′-phosphate as ). Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB References: 1. Cane, D.E., Hsiung, Y., Cornish, J.A., Robinson, J.K and Spenser, I.D. Biosynthesis of vitamine B6: The oxidation of L-threonine 4-phosphate by PdxA. J. Am. Chem. Soc. 120 (1998) 1936– 1937. 2. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B6 biosynthesis: formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D- xylulose-5-phosphate by PdxA and PdxJ protein. FEBS Lett. 449 (1999) 45–48. [PMID: 10225425] 3. Sivaraman, J., Li, Y., Banks, J., Cane, D.E., Matte, A. and Cygler, M. Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway. J. Biol. Chem. 278 (2003) 43682–43690. [PMID: 12896974] [EC 1.1.1.262 created 2000, modified 2006]

EC 1.1.1.289 Common name: sorbose reductase Reaction: D-glucitol + NADP+ = L-sorbose + NADPH + H+ For diagram of reaction, click here Glossary: L-sorbose = L-xylo-hex-2-ulose Other name(s): Sou1p Systematic name: D-glucitol:NADP+ oxidoreductase Comments: The reaction occurs predominantly in the reverse direction. This enzyme can also convert D- into D-mannitol, but more slowly. Belongs in the short-chain dehydrogenase family. References: 1. Greenberg, J.R., Price, N.P., Oliver, R.P., Sherman, F. and Rustchenko, E. Candida albicans SOU1 encodes a sorbose reductase required for L-sorbose utilization. Yeast 22 (2005) 957–969. [PMID: 16134116] 2. Greenberg, J.R., Price, N.P., Oliver, R.P., Sherman, F. and Rustchenko, E. Erratum report: Candida albicans SOU1 encodes a sorbose reductase required for L-sorbose utilization. Yeast 22 (2005) 1171 only. 3. Sugisawa, T., Hoshino, T. and Fujiwara, A. Purification and properties of NADPH-linked L- sorbose reductase from Gluconobacter melanogenus N44-1. Agric. Biol. Chem. 55 (1991) 2043– 2049. 4. Shinjoh, M., Tazoe, M. and Hoshino, T. NADPH-dependent L-sorbose reductase is responsible for L-sorbose assimilation in Gluconobacter suboxydans IFO 3291. J. Bacteriol. 184 (2002) 861– 863. [PMID: 11790761] [EC 1.1.1.289 created 2006]

EC 1.1.1.290 Common name: 4-phosphoerythronate dehydogenase Reaction: 4-phospho-D-erythronate + NAD+ = (3R)-3-hydroxy-2-oxo-4-phosphonooxybutanoate + NADH + H+ For diagram of pyridoxal biosynthesis, click here Other name(s): PdxB; PdxB 4PE dehydrogenase; 4-O-phosphoerythronate dehydrogenase Systematic name: 4-phospho-D-erythronate:NAD+ 2-oxidoreductase Comments: This enzyme catalyses the second step in the biosynthesis of the coenzyme pyridoxal 5′-phosphate in Escherichia coli. The reaction occurs predominantly in the reverse direction [3]. Other enzymes involved in this pathway are EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (pyridoxamine-phosphate oxidase).

References: 1. Lam, H.M. and Winkler, M.E. Metabolic relationships between pyridoxine (vitamin B6) and serine http://www.enzyme-database.org/newenz.php?sp=off Page 3 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

biosynthesis in Escherichia coli K-12. J. Bacteriol. 172 (1990) 6518–6528. [PMID: 2121717] 2. Pease, A.J., Roa, B.R., Luo, W. and Winkler, M.E. Positive growth rate-dependent regulation of the pdxA, ksgA, and pdxB of Escherichia coli K-12. J. Bacteriol. 184 (2002) 1359–1369. [PMID: 11844765] 3. Zhao, G. and Winkler, M.E. A novel α-ketoglutarate reductase activity of the serA-encoded 3- phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria. J. Bacteriol. 178 (1996) 232–239. [PMID: 8550422] 4. Grant, G.A. A new family of 2-hydroxyacid dehydrogenases. Biochem. Biophys. Res. Commun. 165 (1989) 1371–1374. [PMID: 2692566] 5. Schoenlein, P.V., Roa, B.B. and Winkler, M.E. Divergent transcription of pdxB and homology between the pdxB and serA products in Escherichia coli K-12. J. Bacteriol. 171 (1989) 6084–6092. [PMID: 2681152] [EC 1.1.1.290 created 2006]

EC 1.1.99.19 Transferred entry: . Now EC 1.17.99.4, uracil/thymine dehydrogenase [EC 1.1.99.19 created 1961 as EC 1.2.99.1, transferred 1984 to EC 1.1.99.19, deleted 2006]

*EC 1.2.1.10 Common name: acetaldehyde dehydrogenase (acetylating) Reaction: acetaldehyde + CoA + NAD+ = acetyl-CoA + NADH + H+ Other name(s): (acylating); ADA; acylating acetaldehyde dehyrogenase; DmpF Systematic name: acetaldehyde:NAD+ oxidoreductase (CoA-acetylating) Comments: Also acts, more slowly, on glycolaldehyde, propanal and butanal. In Pseudomonas species, this enzyme forms part of a bifunctional enzyme with EC 4.1.3.39, 4-hydroxy-2-oxovalerate aldolase. It is the final enzyme in the meta-cleavage pathway for the degradation of phenols, cresols and catechol, converting the acetaldehyde produced by EC 4.1.3.39 into acetyl-CoA [3]. NADP+ can replace NAD+ but the rate of reaction is much slower [3]. Links to other databases: BRENDA, ERGO, EXPASY, GTD, IUBMB, KEGG, CAS registry number: 9028-91-5 References: 1. Burton, R.M. and Stadtman, E.R. The oxidation of acetaldehyde to acetyl . J. Biol. Chem. 202 (1953) 873–890. [PMID: 13061511] 2. Smith, L.T. and Kaplan, N.O. Purification, properties, and kinetic mechanism of coenzyme A- linked aldehyde dehydrogenase from Clostridium kluyveri. Arch. Biochem. Biophys. 203 (1980) 663–675. [PMID: 7458347] 3. Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. J. Bacteriol. 175 (1993) 377– 385. [PMID: 8419288] [EC 1.2.1.10 created 1961, modified 2006]

EC 1.2.1.71 Common name: succinylglutamate-semialdehyde dehydrogenase + + Reaction: N-succinyl-L-glutamate 5-semialdehyde + NAD + H2O = N-succinyl-L-glutamate + NADH + 2 H For diagram of arginine catabolism, click here Other name(s): succinylglutamic semialdehyde dehydrogenase; N-succinylglutamate 5-semialdehyde dehydrogenase; SGSD; AruD; AstD Systematic name: N-succinyl-L-glutamate 5-semialdehyde:NAD+ oxidoreductase Comments: This is the fourth enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.11 (acetylornithine transaminase), EC 1.2.1.71 (succinylglutamate-semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase) [3,6]. References: 1. Vander Wauven, C., Jann, A., Haas, D., Leisinger, T. and Stalon, V. N2-succinylornithine in ornithine catabolism of Pseudomonas aeruginosa. Arch. Microbiol. 150 (1988) 400–404. [PMID:

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3144259] 2. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882–886. [PMID: 2865249] 3. Tricot, C., Vander Wauven, C., Wattiez, R., Falmagne, P. and Stalon, V. Purification and properties of a succinyltransferase from Pseudomonas aeruginosa specific for both arginine and ornithine. Eur. J. Biochem. 224 (1994) 853–861. [PMID: 7523119] 4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280–7290. [PMID: 9393691] 5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278–4286. [PMID: 9696779] 6. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and of arginine in bacteria. Microbiol. Rev. 50 (1986) 314–352. [PMID: 3534538] 7. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 51 (1987) 178 only. [EC 1.2.1.71 created 2006]

EC 1.2.1.72 Common name: erythrose-4-phosphate dehydrogenase + + Reaction: D-erythrose 4-phosphate + NAD + H2O = 4-phosphoerythronate + NADH + 2 H For diagram of pyridoxal biosynthesis, click here Other name(s): erythrose 4-phosphate dehydrogenase; E4PDH; GapB; Epd dehydrogenase; E4P dehydrogenase Systematic name: D-erythrose 4-phosphate:NAD+ oxidoreductase Comments: This enzyme was originally thought to be a glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12), but this has since been disproved, as glyceraldehyde 3-phosphate is not a substrate [1,2]. Forms part of the pyridoxal-5′-phosphate coenzyme biosynthesis pathway in Escherichia coli, along with EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (pyridoxamine-phosphate oxidase). References: 1. Zhao, G., Pease, A.J., Bharani, N. and Winkler, M.E. Biochemical characterization of gapB- encoded erythrose 4-phosphate dehydrogenase of Escherichia coli K-12 and its possible role in pyridoxal 5′-phosphate biosynthesis. J. Bacteriol. 177 (1995) 2804–2812. [PMID: 7751290] 2. Boschi-Muller, S., Azza, S., Pollastro, D., Corbier, C. and Branlant, G. Comparative enzymatic properties of GapB-encoded erythrose-4-phosphate dehydrogenase of Escherichia coli and phosphorylating glyceraldehyde-3-phosphate dehydrogenase. J. Biol. Chem. 272 (1997) 15106– 15112. [PMID: 9182530] 3. Yang, Y., Zhao, G., Man, T.K. and Winkler, M.E. Involvement of the gapA- and epd (gapB)- encoded dehydrogenases in pyridoxal 5′-phosphate coenzyme biosynthesis in Escherichia coli K-12. J. Bacteriol. 180 (1998) 4294–4299. [PMID: 9696782] [EC 1.2.1.72 created 2006]

EC 1.2.99.1 Transferred entry: now EC 1.17.99.4, uracil/thymine dehydrogenase [EC 1.2.99.1 created 1961, deleted 1984]

*EC 1.3.99.19 Common name: quinoline-4-carboxylate 2-oxidoreductase

Reaction: quinoline-4-carboxylate + acceptor + H2O = 2-oxo-1,2-dihydroquinoline-4-carboxylate + reduced acceptor For diagram of reaction, click here Other name(s): quinaldic acid 4-oxidoreductase; quinoline-4-carboxylate:acceptor 2-oxidoreductase (hydroxylating) Systematic name: quinoline-4-carboxylate:acceptor 2-oxidoreductase (hydroxylating) Comments: A molybdenum—iron—sulfur flavoprotein with molybdopterin cytosine dinucleotide as the molybdenum . Quinoline, 4-methylquinoline and 4-chloroquinoline can also serve as substrates for the enzyme from Agrobacterium sp. 1B. Iodonitrotetrazolium chloride, thionine, menadione and 2,6-dichlorophenolindophenol can act as electron acceptors. http://www.enzyme-database.org/newenz.php?sp=off Page 5 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 175780-18-4 References: 1. Bauer, G. and Lingens, F. Microbial metabolism of quinoline and related compounds. XV. Quinoline-4-carboxylic acid oxidoreductase from Agrobacterium spec.1B: a molybdenum- containing enzyme. Biol. Chem. Hoppe-Seyler 373 (1992) 699–705. [PMID: 1418685] [EC 1.3.99.19 created 1999, modified 2006]

*EC 1.4.3.5 Common name: pyridoxal 5′-phosphate synthase

Reaction: (1) pyridoxamine 5′-phosphate + H2O + O2 = pyridoxal 5′-phosphate + NH3 + H2O2 (2) pyridoxine 5′-phosphate + O2 = pyridoxal 5′-phosphate + H2O2 For diagram of pyridoxal biosynthesis, click here Other name(s): pyridoxamine 5′-phosphate oxidase; pyridoxamine phosphate oxidase; pyridoxine (pyridoxamine)phosphate oxidase; pyridoxine (pyridoxamine) 5′-phosphate oxidase; pyridoxaminephosphate oxidase (EC 1.4.3.5: deaminating); PMP oxidase; pyridoxol-5′- phosphate: oxidoreductase (deaminating) (incorrect); pyridoxamine-phosphate oxidase; PdxH Systematic name: pyridoxamine-5′-phosphate:oxygen oxidoreductase (deaminating) Comments: A flavoprotein (FMN). In Escherichia coli, the coenzyme pyridoxal 5′-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5′-phosphate as substrate). Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 9029-21-4 References: 1. Choi, J.-D., Bowers-Komro, D.M., Davis, M.D., Edmondson, D.E. and McCormick, D.B. Kinetic properties of pyridoxamine (pyridoxine)-5′-phosphate oxidase from rabbit liver. J. Biol. Chem. 258 (1983) 840–845. [PMID: 6822512] 2. Wada, H. and Snell, E.E. The enzymatic oxidation of pyridoxine and pyridoxamine phosphates. J. Biol. Chem. 236 (1961) 2089–2095. [PMID: 13782387] 3. Notheis, C., Drewke, C. and Leistner, E. Purification and characterization of the pyridoxol-5′- phosphate:oxygen oxidoreductase (deaminating) from Escherichia coli. Biochim. Biophys. Acta 1247 (1995) 265–271. [PMID: 7696318] 4. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B6 biosynthesis: formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D- xylulose-5-phosphate by PdxA and PdxJ protein. FEBS Lett. 449 (1999) 45–48. [PMID: 10225425] 5. Musayev, F.N., Di Salvo, M.L., Ko, T.P., Schirch, V. and Safo, M.K. Structure and properties of recombinant human pyridoxine 5′-phosphate oxidase. Protein Sci. 12 (2003) 1455–1463. [PMID: 12824491] 6. Safo, M.K., Musayev, F.N. and Schirch, V. Structure of Escherichia coli pyridoxine 5′-phosphate oxidase in a tetragonal crystal form: insights into the mechanistic pathway of the enzyme. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 599–604. [PMID: 15858270] [EC 1.4.3.5 created 1961, modified 2006]

*EC 1.4.4.2 Common name: glycine dehydrogenase (decarboxylating)

Reaction: glycine + H-protein-lipoyllysine = H-protein-S-aminomethyldihydrolipoyllysine + CO2 For diagram of the glycine cleavage system, click here Glossary: dihydrolipoyl group Other name(s): P-protein; glycine decarboxylase; glycine-cleavage complex; glycine:lipoylprotein oxidoreductase (decarboxylating and acceptor-aminomethylating); protein P1 Systematic name: glycine:H-protein-lipoyllysine oxidoreductase (decarboxylating, acceptor-amino-methylating) Comments: A pyridoxal-phosphate protein. A component, with EC 2.1.2.10, aminomethyltransferase and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, previously known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3]. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, CAS registry number: 37259-67-9

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References: 1. Hiraga, K. and Kikuchi, G. The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein. J. Biol. Chem. 255 (1980) 11671–11676. [PMID: 7440563] 2. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] 3. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [PMID: 15642479] [EC 1.4.4.2 created 1984, modified 2003, modified 2006]

EC 1.7.1.13 Common name: queuine synthase Reaction: queuine + 2 NADP+ = 7-cyano-7-carbaguanine + 2 NADPH + 2 H+ For diagram of reaction, click here

Glossary: queuine = 7-aminomethyl-7-carbaguanine = preQ1

Other name(s): YkvM; QueF; preQ0 reductase; preQ0 oxidoreductase; 7-cyano-7-deazaguanine reductase; 7- aminomethyl-7-carbaguanine:NADP+ oxidoreductase Systematic name: queuine:NADP+ oxidoreductase Comments: The reaction occurs in the reverse direction. This enzyme catalyses one of the early steps in the synthesis of queosine (Q-tRNA), and is followed by the action of EC 2.4.2.29, queuine tRNA- ribosyltransferase. Queosine is found in the wobble position of tRNAGUN in Eukarya and Bacteria [2] and is thought to be involved in translational modulation. The enzyme is not a GTP cyclohydrolase, as was thought previously based on sequence-homology studies. References: 1. Van Lanen, S.G., Reader, J.S., Swairjo, M.A., de Crécy-Lagard, V., Lee, B. and Iwata-Reuyl, D. From cyclohydrolase to oxidoreductase: discovery of nitrile reductase activity in a common fold. Proc. Natl. Acad. Sci. USA 102 (2005) 4264–4269. [PMID: 15767583] 2. Yokoyama, S., Miyazawa, T., Iitaka, Y., Yamaizumi, Z., Kasai, H. and Nishimura, S. Three- dimensional structure of hyper-modified nucleoside Q located in the wobbling position of tRNA. Nature 282 (1979) 107–109. [PMID: 388227] 3. Kuchino, Y., Kasai, H., Nihei, K. and Nishimura, S. Biosynthesis of the modified nucleoside Q in transfer RNA. Nucleic Acids Res. 3 (1976) 393–398. [PMID: 1257053] 4. Okada, N., Noguchi, S., Nishimura, S., Ohgi, T., Goto, T., Crain, P.F. and McCloskey, J.A. Structure determination of a nucleoside Q precursor isolated from E. coli tRNA: 7-(aminomethyl)- 7-deazaguanosine. Nucleic Acids Res. 5 (1978) 2289–2296. [PMID: 353740] 5. Noguchi, S., Yamaizumi, Z., Ohgi, T., Goto, T., Nishimura, Y., Hirota, Y. and Nishimura, S. Isolation of Q nucleoside precursor present in tRNA of an E. coli mutant and its characterization as 7-(cyano)-7-deazaguanosine. Nucleic Acids Res. 5 (1978) 4215–4223. [PMID: 364423] 6. Swairjo, M.A., Reddy, R.R., Lee, B., Van Lanen, S.G., Brown, S., de Crécy-Lagard, V., Iwata- Reuyl, D. and Schimmel, P. Crystallization and preliminary X-ray characterization of the nitrile reductase QueF: a queuosine-biosynthesis enzyme. Acta Crystallogr. F Struct. Biol. Crystal. Co 61 (2005) 945–948. [EC 1.7.1.13 created 2006]

*EC 1.8.1.4 Common name: dihydrolipoyl dehydrogenase Reaction: protein 6-N-(dihydrolipoyl)lysine + NAD+ = protein 6-N-(lipoyl)lysine + NADH + H+ For diagram of oxo-acid dehydrogenase complexes, click here, for diagram of the citric-acid cycle, click here and for diagram of the glycine-cleavage system, click here Glossary: dihydrolipoyl group Other name(s): LDP-Glc; LDP-Val; dehydrolipoate dehydrogenase; diaphorase; dihydrolipoamide dehydrogenase; dihydrolipoamide:NAD+ oxidoreductase; dihydrolipoic dehydrogenase; dihydrothioctic dehydrogenase; lipoamide dehydrogenase (NADH); lipoamide oxidoreductase (NADH); lipoamide reductase; lipoamide reductase (NADH); lipoate dehydrogenase; dehydrogenase; lipoyl dehydrogenase; protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase Systematic name: protein-6-N-(dihydrolipoyl)lysine:NAD+ oxidoreductase Comments: A flavoprotein (FAD). A component of the multienzyme 2-oxo-acid dehydrogenase complexes. In the complex, it binds to the core of EC 2.3.1.12, dihydrolipoyllysine- http://www.enzyme-database.org/newenz.php?sp=off Page 7 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

residue acetyltransferase, and catalyses oxidation of its dihydrolipoyl groups. It plays a similar role in the oxoglutarate and 3-methyl-2-oxobutanoate dehydrogenase complexes. Another substrate is the dihydrolipoyl group in the H-protein of the glycine-cleavage system (click here for diagram), in which it acts, together with EC 1.4.4.2, glycine dehydrogenase (decarboxylating), and EC 2.1.2.10, aminomethyltransferase, to break down glycine. It can also use free dihydrolipoate, dihydrolipoamide or dihydrolipoyllysine as substrate. This enzyme was first shown to catalyse the oxidation of NADH by methylene blue; this activity was called diaphorase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [6]. Links to other databases: BRENDA, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 9001-18-7 References: 1. Massey, V. Lipoyl dehydrogenase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 275–306. 2. Massey, V., Gibson, Q.H. and Veeger, C. Intermediates in the catalytic action of lipoyl dehydrogenase (diaphorase). Biochem. J. 77 (1960) 341–351. [PMID: 13767908] 3. Savage, N. Preparation and properties of highly purified diaphorase. Biochem. J. 67 (1957) 146– 155. [PMID: 13471525] 4. Straub, F.B. Isolation and properties of a flavoprotein from heart muscle tissue. Biochem. J. 33 (1939) 787–792. 5. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] 6. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [PMID: 15642479] [EC 1.8.1.4 created 1961 as EC 1.6.4.3, modified 1976, transferred 1983 to EC 1.8.1.4, modified 2003, modified 2006]

*EC 1.11.1.14 Common name: lignin peroxidase

Reaction: 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol + H2O2 = 3,4-dimethoxybenzaldehyde + 1-(3,4- dimethoxyphenyl)ethane-1,2-diol + H2O For diagram of reaction, click here Other name(s): diarylpropane oxygenase; ligninase I; diarylpropane peroxidase; LiP; diarylpropane:oxygen,hydrogen-peroxide oxidoreductase (C-C-bond-cleaving) Systematic name: 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol:hydrogen-peroxide oxidoreductase Comments: A hemoprotein. Brings about the oxidative cleavage of C-C and ether (C-O-C) bonds in a number of lignin model compounds (of the diarylpropane and arylpropane-aryl ether type). The enzyme also oxidizes benzyl alcohols to aldehydes, via an aromatic cation radical [9]. Involved in the oxidative breakdown of lignin in white rot basidiomycetes. Molecular oxygen may be involved in the reaction of substrate radicals under aerobic conditions [3,8]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 93792-13-3 References: 1. Paszczynski, A., Huynh, V.-B. and Crawford, R. Comparison of ligninase-I and peroxidase-M2 from the white-rot fungus Phanerochaete chrysosporium. Arch. Biochem. Biophys. 244 (1986) 750–765. [PMID: 3080953] 2. Renganathan, V., Miki, K. and Gold, M.H. Multiple molecular forms of diarylpropane oxygenase, an H2O2-requiring, lignin-degrading enzyme from Phanerochaete chrysosporium. Arch. Biochem. Biophys. 241 (1985) 304–314. [PMID: 4026322] 3. Tien, M. and Kirk, T.T. Lignin-degrading enzyme from Phanerochaete chrysosporium; purification, characterization, and catalytic properties of a unique H2O2-requiring oxygenase. Proc. Natl. Acad. Sci. USA 81 (1984) 2280–2284. 4. Doyle, W.A., Blodig, W., Veitch, N.C., Piontek, K. and Smith, A.T. Two substrate interaction sites in lignin peroxidase revealed by site-directed mutagenesis. Biochemistry 37 (1998) 15097– 15105. [PMID: 9790672] 5. Wariishi, H., Marquez, L., Dunford, H.B. and Gold, M.H. Lignin peroxidase compounds II and III. Spectral and kinetic characterization of reactions with peroxides. J. Biol. Chem. 265 (1990) 11137–11142. [PMID: 2162833] 6. Cai, D.Y. and Tien, M. Characterization of the oxycomplex of lignin peroxidases from Phanerochaete chrysosporium: equilibrium and kinetics studies. Biochemistry 29 (1990) 2085– 2091. [PMID: 2328240] 7. Tien, M. and Tu, C.P. Cloning and sequencing of a cDNA for a ligninase from Phanerochaete chrysosporium. Nature 326 (1987) 520–523. [PMID: 3561490] 8. Renganathan, V., Miki, K. and Gold, M.H. Role of molecular oxygen in lignin peroxidase reactions. Arch. Biochem. Biophys. 246 (1986) 155–161. [PMID: 3754412] http://www.enzyme-database.org/newenz.php?sp=off Page 8 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

9. Kersten, P.J., Tien, M., Kalyanaraman, B. and Kirk, T.K. The ligninase of Phanerochaete chrysosporium generates cation radicals from methoxybenzenes. J. Biol. Chem. 260 (1985) 2609–2612. [PMID: 2982828] 10. Kirk, T.K. and Farrell, R.L. Enzymatic "combustion": the microbial degradation of lignin. Annu. Rev. Microbiol. 41 (1987) 465–505. [PMID: 3318677] [EC 1.11.1.14 created 1992, modified 2006]

EC 1.11.1.16 Common name: versatile peroxidase

Reaction: (1) Reactive Black 5 + H2O2 = oxidized Reactive Black 5 + 2 H2O (2) donor + H2O2 = oxidized donor + 2 H2O Glossary: reactive black 5 = tetrasodium 4-amino-5-hydroxy-3,6(bis(4-(2- (sulfonatooxy)ethylsulfonyl)phenyl)azo)-naphthalene-2,7-disulfonate Other name(s): VP; hybrid peroxidase; polyvalent peroxidase Systematic name: reactive-black-5:hydrogen-peroxide oxidoreductase Comments: A hemoprotein. This ligninolytic peroxidase combines the substrate-specificity characteristics of the two other ligninolytic peroxidases, EC 1.11.1.13, and EC 1.11.1.14, lignin peroxidase. It is also able to oxidize phenols, hydroquinones and both low- and high-redox- potential dyes, due to a hybrid molecular architecture that involves multiple binding sites for substrates [2,4]. References: 1. Martínez, M.J., Ruiz-Dueñas, F.J., Guillén, F. and Martínez, A.T. Purification and catalytic properties of two manganese peroxidase isoenzymes from Pleurotus eryngii. Eur. J. Biochem. 237 (1996) 424–432. [PMID: 8647081] 2. Heinfling, A., Ruiz-Dueñas, F.J., Martínez, M.J., Bergbauer, M., Szewzyk, U. and Martínez, A.T. A study on reducing substrates of manganese-oxidizing peroxidases from Pleurotus eryngii and Bjerkandera adusta. FEBS Lett. 428 (1998) 141–146. [PMID: 9654123] 3. Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Molecular characterization of a novel peroxidase isolated from the ligninolytic fungus Pleurotus eryngii. Mol. Microbiol. 31 (1999) 223– 235. [PMID: 9987124] 4. Camarero, S., Sarkar, S., Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Description of a versatile peroxidase involved in the natural degradation of lignin that has both manganese peroxidase and lignin peroxidase substrate interaction sites. J. Biol. Chem. 274 (1999) 10324– 10330. [PMID: 10187820] 5. Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Heterologous expression of Pleurotus eryngii peroxidase confirms its ability to oxidize Mn2+ and different aromatic substrates. Appl. Environ. Microbiol. 65 (1999) 4705–4707. [PMID: 10508113] 6. Camarero, S., Ruiz-Dueñas, F.J., Sarkar, S., Martínez, M.J. and Martínez, A.T. The cloning of a new peroxidase found in lignocellulose cultures of Pleurotus eryngii and sequence comparison with other fungal peroxidases. FEMS Microbiol. Lett. 191 (2000) 37–43. [PMID: 11004397] 7. Ruiz-Dueñas, F.J., Camarero, S., Pérez-Boada, M., Martínez, M.J. and Martínez, A.T. A new versatile peroxidase from Pleurotus. Biochem. Soc. Trans. 29 (2001) 116–122. [PMID: 11356138] 8. Banci, L., Camarero, S., Martínez, A.T., Martínez, M.J., Pérez-Boada, M., Pierattelli, R. and Ruiz-Dueñas, F.J. NMR study of manganese(II) binding by a new versatile peroxidase from the white-rot fungus Pleurotus eryngii. J. Biol. Inorg. Chem. 8 (2003) 751–760. [PMID: 12884090] 9. Pérez-Boada, M., Ruiz-Dueñas, F.J., Pogni, R., Basosi, R., Choinowski, T., Martínez, M.J., Piontek, K. and Martínez, A.T. Versatile peroxidase oxidation of high redox potential aromatic compounds: site-directed mutagenesis, spectroscopic and crystallographic investigation of three long-range electron transfer pathways. J. Mol. Biol. 354 (2005) 385–402. [PMID: 16246366] 10. Caramelo, L., Martínez, M.J. and Martínez, A.T. A search for ligninolytic peroxidases in the fungus Pleurotus eryngii involving α-keto-γ-thiomethylbutyric acid and lignin model dimer. Appl. Environ. Microbiol. 65 (1999) 916–922. [PMID: 10049842] [EC 1.11.1.16 created 2006]

*EC 1.13.11.11 Common name: tryptophan 2,3-dioxygenase

Reaction: L-tryptophan + O2 = N-formyl-L-kynurenine For diagram of tryptophan catabolism, click here Other name(s): tryptophan pyrrolase (ambiguous); ; tryptophan oxygenase; tryptamine 2,3-

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dioxygenase; tryptophan peroxidase; indoleamine 2,3-dioxygenase (ambiguous); indolamine 2,3- dioxygenase (ambiguous); L-tryptophan pyrrolase; TDO; L-tryptophan 2,3-dioxygenase Systematic name: L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing) Comments: A protohemoprotein. In mammals, the enzyme appears to be located only in the liver. This enzyme, together with EC 1.13.11.52, indoleamine 2,3-dioxygenase, catalyses the first and rate-limiting step in the kynurenine pathway, the major pathway of tryptophan metabolism [5]. The enzyme is specific for tryptophan as substrate, but is far more active with L-tryptophan than with D-tryptophan [2]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 9014-51-1 References: 1. Uchida, K., Shimizu, T., Makino, R., Sakaguchi, K., Iizuka, T., Ishimura, Y., Nozawa, T. and Hatano, M. Magnetic and natural circular dichroism of L-tryptophan 2,3-dioxygenases and indoleamine 2,3-dioxygenase. I. Spectra of ferric and ferrous high spin forms. J. Biol. Chem. 258 (1983) 2519–2525. [PMID: 6600455] 2. Ren, S., Liu, H., Licad, E. and Correia, M.A. Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme. Arch. Biochem. Biophys. 333 (1996) 96–102. [PMID: 8806758] 3. Leeds, J.M., Brown, P.J., McGeehan, G.M., Brown, F.K. and Wiseman, J.S. Isotope effects and alternative substrate reactivities for tryptophan 2,3-dioxygenase. J. Biol. Chem. 268 (1993) 17781–17786. [PMID: 8349662] 4. Dang, Y., Dale, W.E. and Brown, O.R. Comparative effects of oxygen on indoleamine 2,3- dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway. Free Radic. Biol. Med. 28 (2000) 615–624. [PMID: 10719243] 5. Littlejohn, T.K., Takikawa, O., Truscott, R.J. and Walker, M.J. Asp274 and His346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase. J. Biol. Chem. 278 (2003) 29525–29531. [PMID: 12766158] [EC 1.13.11.11 created 1961 as EC 1.11.1.4, deleted 1964, reinstated 1965 as EC 1.13.1.12, transferred 1972 to EC 1.13.11.11, modified 1989, modified 2006]

*EC 1.13.11.19 Common name: cysteamine dioxygenase

Reaction: 2-aminoethanethiol + O2 = hypotaurine For diagram of taurine biosynthesis, click here Other name(s): persulfurase; cysteamine oxygenase; cysteamine:oxygen oxidoreductase Systematic name: 2-aminoethanethiol:oxygen oxidoreductase Comments: A non-heme iron protein that is involved in the biosynthesis of taurine. Requires catalytic amounts of a cofactor-like compound, such as sulfur, sufide, selenium or methylene blue for maximal activity. 3-Aminopropanethiol (homocysteamine) and 2-mercaptoethanol can also act as substrates, but , cysteine, and cysteine ethyl- and methyl esters are not good substrates [1,3]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 9033-41-4 References: 1. Cavallini, D., de Marco, C., Scandurra, R., Duprè, S. and Graziani, M.T. The enzymatic oxidation of cysteamine to hypotaurine. Purification and properties of the enzyme. J. Biol. Chem. 241 (1966) 3189–3196. [PMID: 5912113] 2. Wood, J.L. and Cavallini, D. Enzymic oxidation of cysteamine to hypotaurine in the absence of a cofactor. Arch. Biochem. Biophys. 119 (1967) 368–372. [PMID: 6052430] 3. Cavallini, D., Federici, G., Ricci, G., Duprè, S. and Antonucci, A. The specificity of cysteamine oxygenase. FEBS Lett. 56 (1975) 348–351. [PMID: 1157952] 4. Richerson, R.B. and Ziegler, D.M. Cysteamine dioxygenase. Methods Enzymol. 143 (1987) 410– 415. [PMID: 3657558] [EC 1.13.11.19 created 1972, modified 2006]

EC 1.13.11.42 Deleted entry: indoleamine- 2,3-dioxygenase [EC 1.13.11.42 created 1992, deleted 2006]

EC 1.13.11.52 Common name: indoleamine 2,3-dioxygenase

Reaction: (1) D-tryptophan + O2 = N-formyl-D-kynurenine

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(2) L-tryptophan + O2 = N-formyl-L-kynurenine For diagram of tryptophan catabolism, click here Other name(s): IDO (ambiguous); tryptophan pyrrolase (ambiguous) Systematic name: D-tryptophan:oxygen 2,3-oxidoreductase (decyclizing) Comments: A protohemoprotein. Requires ascorbic acid and methylene blue for activity. This enzyme has broader substrate specificity than EC 1.13.11.11, tryptophan 2,3-dioxygenase [1]. It is induced in response to pathological conditions and host-defense mechanisms and its distribution in mammals is not confined to the liver [2]. While the enzyme is more active with D-tryptophan than L- tryptophan, its only known function to date is in the metabolism of L-tryptophan [2,6]. Superoxide radicals can replace O2 as oxygen donor [4,7]. References: 1. Yamamoto, S. and Hayaishi, O. Tryptophan pyrrolase of rabbit intestine. D- and L-tryptophan- cleaving enzyme or enzymes. J. Biol. Chem. 242 (1967) 5260–5266. [PMID: 6065097] 2. Yasui, H., Takai, K., Yoshida, R. and Hayaishi, O. Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients. Proc. Natl. Acad. Sci. USA 83 (1986) 6622–6626. [PMID: 2428037] 3. Takikawa, O., Yoshida, R., Kido, R. and Hayaishi, O. Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. J. Biol. Chem. 261 (1986) 3648–3653. [PMID: 2419335] 4. Hirata, F., Ohnishi, T. and Hayaishi, O. Indoleamine 2,3-dioxygenase. Characterization and - properties of enzyme. O2 complex. J. Biol. Chem. 252 (1977) 4637–4642. [PMID: 194886] 5. Dang, Y., Dale, W.E. and Brown, O.R. Comparative effects of oxygen on indoleamine 2,3- dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway. Free Radic. Biol. Med. 28 (2000) 615–624. [PMID: 10719243] 6. Littlejohn, T.K., Takikawa, O., Truscott, R.J. and Walker, M.J. Asp274 and His346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase. J. Biol. Chem. 278 (2003) 29525–29531. [PMID: 12766158] 7. Thomas, S.R. and Stocker, R. Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox Rep. 4 (1999) 199–220. [PMID: 10731095] 8. Sono, M. Spectroscopic and equilibrium studies of ligand and organic substrate binding to indolamine 2,3-dioxygenase. Biochemistry 29 (1990) 1451–1460. [PMID: 2334706] [EC 1.13.11.52 created 2006]

EC 1.13.11.53 Common name: acireductone dioxygenase (Ni2+-requiring)

Reaction: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O2 = 3-(methylthio)propanoate + formate + CO For diagram of methione-salvage pathway, click here and for mechanism of reaction, click here Glossary: acireductone = 1,2-dihydroxy-5-(methylthio)-pent-1-en-3-one Other name(s): ARD; 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase (ambiguous); acireductone dioxygenase (ambiguous); E-2 Systematic name: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one:oxygen oxidoreductase (formate- and CO-forming) Comments: Requires Ni2+. If iron(II) is bound instead of Ni2+, the reaction catalysed by EC 1.13.11.54, acireductone dioxygenase [iron(II)-requiring], occurs instead [1]. The enzyme from the bacterium Klebsiella oxytoca (formerly Klebsiella pneumoniae) ATCC strain 8724 is involved in the salvage pathway. References: 1. Wray, J.W. and Abeles, R.H. A bacterial enzyme that catalyzes formation of carbon monoxide. J. Biol. Chem. 268 (1993) 21466–21469. [PMID: 8407993] 2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in Klebsiella pneumoniae and rat liver. Identification and characterization of two novel dioxygenases. J. Biol. Chem. 270 (1995) 3147–3153. [PMID: 7852397] 3. Furfine, E.S. and Abeles, R.H. Intermediates in the conversion of 5′-S-methylthioadenosine to methionine in Klebsiella pneumoniae. J. Biol. Chem. 263 (1988) 9598–9606. [PMID: 2838472] 4. Dai, Y., Wensink, P.C. and Abeles, R.H. One protein, two enzymes. J. Biol. Chem. 274 (1999) 1193–1195. [PMID: 9880484] 5. Mo, H., Dai, Y., Pochapsky, S.S. and Pochapsky, T.C. 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J. Biomol. NMR 14 (1999) 287–288. [PMID: 10481280] 6. Dai, Y., Pochapsky, T.C. and Abeles, R.H. Mechanistic studies of two dioxygenases in the methionine salvage pathway of Klebsiella pneumoniae. Biochemistry 40 (2001) 6379–6387. [PMID: 11371200] 7. Al-Mjeni, F., Ju, T., Pochapsky, T.C. and Maroney, M.J. XAS investigation of the structure and function of Ni in acireductone dioxygenase. Biochemistry 41 (2002) 6761–6769. [PMID: http://www.enzyme-database.org/newenz.php?sp=off Page 11 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

12022880] 8. Pochapsky, T.C., Pochapsky, S.S., Ju, T., Mo, H., Al-Mjeni, F. and Maroney, M.J. Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae. Nat. Struct. Biol. 9 (2002) 966–972. [PMID: 12402029] [EC 1.13.11.53 created 2006]

EC 1.13.11.54 Common name: acireductone dioxygenase [iron(II)-requiring]

Reaction: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one + O2 = 4-(methylthio)-2-oxobutanoate + formate For diagram of methione-salvage pathway, click here and for mechanism of reaction, click here Other name(s): ARD′; 2-hydroxy-3-keto-5-thiomethylpent-1-ene dioxygenase (ambiguous); acireductone dioxygenase (ambiguous); E-2′; E-3 dioxygenase Systematic name: 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one:oxygen oxidoreductase (formate-forming) Comments: Requires iron(II). If Ni2+ is bound instead of iron(II), the reaction catalysed by EC 1.13.11.53, acireductone dioxygenase (Ni2+-requiring), occurs instead. The enzyme from the bacterium Klebsiella oxytoca (formerly Klebsiella pneumoniae) ATCC strain 8724 is involved in the methionine salvage pathway. References: 1. Wray, J.W. and Abeles, R.H. A bacterial enzyme that catalyzes formation of carbon monoxide. J. Biol. Chem. 268 (1993) 21466–21469. [PMID: 8407993] 2. Wray, J.W. and Abeles, R.H. The methionine salvage pathway in Klebsiella pneumoniae and rat liver. Identification and characterization of two novel dioxygenases. J. Biol. Chem. 270 (1995) 3147–3153. [PMID: 7852397] 3. Furfine, E.S. and Abeles, R.H. Intermediates in the conversion of 5′-S-methylthioadenosine to methionine in Klebsiella pneumoniae. J. Biol. Chem. 263 (1988) 9598–9606. [PMID: 2838472] 4. Dai, Y., Wensink, P.C. and Abeles, R.H. One protein, two enzymes. J. Biol. Chem. 274 (1999) 1193–1195. [PMID: 9880484] 5. Mo, H., Dai, Y., Pochapsky, S.S. and Pochapsky, T.C. 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J. Biomol. NMR 14 (1999) 287–288. [PMID: 10481280] 6. Dai, Y., Pochapsky, T.C. and Abeles, R.H. Mechanistic studies of two dioxygenases in the methionine salvage pathway of Klebsiella pneumoniae. Biochemistry 40 (2001) 6379–6387. [PMID: 11371200] 7. Al-Mjeni, F., Ju, T., Pochapsky, T.C. and Maroney, M.J. XAS investigation of the structure and function of Ni in acireductone dioxygenase. Biochemistry 41 (2002) 6761–6769. [PMID: 12022880] 8. Pochapsky, T.C., Pochapsky, S.S., Ju, T., Mo, H., Al-Mjeni, F. and Maroney, M.J. Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae. Nat. Struct. Biol. 9 (2002) 966–972. [PMID: 12402029] [EC 1.13.11.54 created 2006]

EC 1.13.11.55 Common name: sulfur oxygenase/reductase + Reaction: 4 sulfur + 4 H2O + O2 = 2 hydrogen sulfide + 2 bisulfite + 2 H Other name(s): SOR; sulfur oxygenase; sulfur oxygenase reductase Systematic name: sulfur:oxygen oxidoreductase (hydrogen-sulfide- and sulfite-forming) Comments: This enzyme, which is found in thermophilic microorganisms, contains one mononuclear none- heme iron centre per subunit. Elemental sulfur is both the electron donor and one of the two known acceptors, the other being oxygen. Another reaction product is thiosulfate, but this is probably formed non-enzymically at elevated temperature from sulfite and sulfur [1]. This enzyme differs from EC 1.13.11.18, and EC 1.97.1.3, sulfur reductase, in that both activities are found together. References: 1. Kletzin, A. Coupled enzymatic production of sulfite, thiosulfate, and hydrogen sulfide from sulfur: purification and properties of a sulfur oxygenase reductase from the facultatively anaerobic archaebacterium Desulfurolobus ambivalens. J. Bacteriol. 171 (1989) 1638–1643. [PMID: 2493451] 2. Kletzin, A. Molecular characterization of the sor gene, which encodes the sulfur oxygenase/reductase of the thermoacidophilic Archaeum Desulfurolobus ambivalens. J. Bacteriol. 174 (1992) 5854–5859. [PMID: 1522063] 3. Sun, C.W., Chen, Z.W., He, Z.G., Zhou, P.J. and Liu, S.J. Purification and properties of the sulfur http://www.enzyme-database.org/newenz.php?sp=off Page 12 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

oxygenase/reductase from the acidothermophilic archaeon, Acidianus strain S5. Extremophiles 7 (2003) 131–134. [PMID: 12664265] 4. Urich, T., Bandeiras, T.M., Leal, S.S., Rachel, R., Albrecht, T., Zimmermann, P., Scholz, C., Teixeira, M., Gomes, C.M. and Kletzin, A. The sulphur oxygenase reductase from Acidianus ambivalens is a multimeric protein containing a low-potential mononuclear non-haem iron centre. Biochem. J. 381 (2004) 137–146. [PMID: 15030315] [EC 1.13.11.55 created 2006]

EC 1.13.12.14 Common name: chlorophyllide-a oxygenase + + Reaction: (1) chlorophyllide a + O2 + NADPH + H = 7-hydroxychlorophyllide a + H2O + NADP + + (2) 7-hydroxychlorophyllide a + O2 + NADPH + H = chlorophyllide b + 2 H2O + NADP Other name(s): chlorophyllide a oxygenase; cholorophyll-b synthase; CAO Systematic name: chlorophyllide-a:oxygen 7-oxidoreductase Comments: b is required for the assembly of stable light-harvesting complexes (LHCs) in the of green , cyanobacteria and plants [2,3]. Contains a mononuclear iron centre [3]. The enzyme catalyses two successive hydroxylations at the 7-methyl group of chlorophyllide a. The second step yields the aldehyde hydrate, which loses H2O spontaneously to form chlorophyllide b [2]. and protochlorophyllide a are not substrates [2]. References: 1. Espineda, C.E., Linford, A.S., Devine, D. and Brusslan, J.A. The AtCAO gene, encoding chlorophyll a oxygenase, is required for synthesis in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 96 (1999) 10507–10511. [PMID: 10468639] 2. Oster, U., Tanaka, R., Tanaka, A. and Rudiger, W. Cloning and functional expression of the gene encoding the key enzyme for chlorophyll b biosynthesis (CAO) from Arabidopsis thaliana. Plant J. 21 (2000) 305–310. [PMID: 10758481] 3. Eggink, L.L., LoBrutto, R., Brune, D.C., Brusslan, J., Yamasato, A., Tanaka, A. and Hoober, J.K. Synthesis of chlorophyll b: localization of chlorophyllide a oxygenase and discovery of a stable radical in the catalytic subunit. BMC Plant Biol. 4 (2004) 5 only. [PMID: 15086960] 4. Porra, R.J., Schafer, W., Cmiel, E., Katheder, I. and Scheer, H. The derivation of the formyl- group oxygen of chlorophyll b in higher plants from molecular oxygen. Achievement of high 18 enrichment of the 7-formyl-group oxygen from O2 in greening maize leaves. Eur. J. Biochem. 219 (1994) 671–679. [PMID: 8307032] [EC 1.13.12.14 created 2006]

EC 1.14.13.65 Deleted entry: 2-hydroxyquinoline 8-monooxygenase [EC 1.14.13.65 created 1999, deleted 2006]

EC 1.14.13.101 Common name: senecionine N-oxygenase + + Reaction: senecionine + NADPH + H + O2 = senecionine N-oxide + NADP + H2O Other name(s): senecionine monooxygenase (N-oxide-forming); SNO Systematic name: senecionine,NADPH:oxygen oxidoreductase (N-oxide-forming) Comments: A flavoprotein. NADH cannot replace NADPH. While pyrrolizidine alkaloids of the senecionine and monocrotaline types are generally good substrates (e.g. senecionine, retrorsine and monocrotaline), the enzyme does not use ester alkaloids lacking an hydroxy group at C-7 (e.g. supinine and phalaenopsine), 1,2-dihydro-alkaloids (e.g. sarracine) or unesterified necine bases (e.g. senkirkine) as substrates [1]. Senecionine N-oxide is used by insects as a chemical defense: senecionine N- oxide is non-toxic, but it is bioactivated to a toxic form by the action of P-450 oxidase when absorbed by insectivores. Links to other databases: CAS registry number: 220581-68-0 References: 1. Lindigkeit, R., Biller, A., Buch, M., Schiebel, H.M., Boppre, M. and Hartmann, T. The two facies of pyrrolizidine alkaloids: the role of the tertiary amine and its N-oxide in chemical defense of insects with acquired plant alkaloids. Eur. J. Biochem. 245 (1997) 626–636. [PMID: 9182998] 2. Naumann, C., Hartmann, T. and Ober, D. Evolutionary recruitment of a flavin-dependent monooxygenase for the detoxification of host plant-acquired pyrrolizidine alkaloids in the

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alkaloid-defended arctiid moth Tyria jacobaeae. Proc. Natl. Acad. Sci. USA 99 (2002) 6085– 6090. [PMID: 11972041] [EC 1.14.13.101 created 2006]

*EC 1.14.99.3 Common name: 2+ Reaction: heme + 3 AH2 + 3 O2 = + Fe + CO + 3 A + 3 H2O For diagram of the reaction mechanism, click here Other name(s): ORP33 proteins; haem oxygenase; heme oxygenase (decyclizing); heme oxidase; haem oxidase Systematic name: heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating) Comments: Requires NAD(P)H and EC 1.6.2.4, NADPH—hemoprotein reductase. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the α-carbon to CO. The central iron is kept in the reduced state by NAD(P)H. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 9059-22-7 References: 1. Maines, M.D., Ibrahim, N.G. and Kappas, K. Solubilization and partial purification of heme oxygenase from rat liver. J. Biol. Chem. 252 (1977) 5900–5903. [PMID: 18477] 2. Sunderman, F.W., Jr., Downs, J.R., Reid, M.C. and Bibeau, L.M. Gas-chromatographic assay for heme oxygenase activity. Clin. Chem. 28 (1982) 2026–2032. [PMID: 6897023] 3. Yoshida, T., Takahashi, S. and Kikuchi, J. Partial purification and reconstitution of the heme oxygenase system from pig spleen microsomes. J. Biochem. (Tokyo) 75 (1974) 1187–1191. [PMID: 4370250] 4. Noguchi, M., Yoshida, T. and Kikuchi, G. Specific requirement of NADPH-cytochrome c reductase for the microsomal heme oxygenase reaction yielding biliverdin IX α. FEBS Lett. 98 (1979) 281–284. [PMID: 105935] 5. Lad, L., Schuller, D.J., Shimizu, H., Friedman, J., Li, H., Ortiz de Montellano, P.R. and Poulos, T.L. Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1. J. Biol. Chem. 278 (2003) 7834–7843. [PMID: 12500973] [EC 1.14.99.3 created 1972, modified 2006]

EC 1.17.99.4 Common name: uracil/thymine dehydrogenase

Reaction: (1) uracil + H2O + acceptor = barbiturate + reduced acceptor (2) thymine + H2O + acceptor = 5-methylbarbiturate + reduced acceptor For diagram of pyrimidine catabolism, click here Other name(s): uracil oxidase; uracil-thymine oxidase; uracil dehydrogenase Systematic name: uracil:acceptor oxidoreductase Comments: Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with EC 3.5.2.1 (barbiturase) and EC 3.5.1.95 (N-malonylurea hydrolase). Mammals, plants and other microorganisms utilize the reductive pathway, comprising EC 1.3.1.1 [dihydrouracil dehydrogenase (NAD+)] or EC 1.3.1.2 [dihydropyrimidine dehydrogenase (NADP+)], EC 3.5.2.2 () and EC 3.5.1.6 (β-ureidopropionase), with the ultimate degradation products being an L-amino acid, NH3 and CO2 [5]. Links to other databases: CAS registry number: 9029-00-9 References: 1. Hayaishi, O. and Kornberg, A. Metabolism of cytosine, thymine, uracil, and barbituric acid by bacterial enzymes. J. Biol. Chem. 197 (1952) 717–723. [PMID: 12981104] 2. Wang, T.P. and Lampen, J.O. Metabolism of pyrimidines by a soil bacterium. J. Biol. Chem. 194 (1952) 775–783. [PMID: 14927671] 3. Wang, T.P. and Lampen, J.O. Uracil oxidase and the isolation of barbituric acid from uracil oxidation. J. Biol. Chem. 194 (1952) 785–791. [PMID: 14927672] 4. Lara, F.J.S. On the decomposition of pyrimidines by bacteria. II. Studies with cell-free enzyme preparations. J. Bacteriol. 64 (1952) 279–285. [PMID: 14955523] 5. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme, ureidomalonase. Biochem. Biophys. Res. Commun. 286 (2001) 222–226. [PMID: 11485332] [EC 1.17.99.4 created 1961 as EC 1.2.99.1, transferred 1984 to EC 1.1.99.19, transferred 2006 to EC 1.17.99.4]

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*EC 2.1.2.10 Common name: aminomethyltransferase Reaction: [protein]-S8-aminomethyldihydrolipoyllysine + tetrahydrofolate = [protein]-dihydrolipoyllysine + 5,10- methylenetetrahydrofolate + NH3 For diagram of the glycine-cleavage system, click here Glossary: dihydrolipoyl group Other name(s): S-aminomethyldihydrolipoylprotein:(6S)-tetrahydrofolate aminomethyltransferase (ammonia- forming); T-protein; glycine synthase; tetrahydrofolate aminomethyltransferase Systematic name: [protein]-S8-aminomethyldihydrolipoyllysine:tetrahydrofolate aminomethyltransferase (ammonia- forming) Comments: A component, with EC 1.4.4.2 glycine dehydrogenase (decarboxylating) and EC 1.8.1.4, dihydrolipoyl dehydrogenanse, of the glycine cleavage system, formerly known as glycine synthase. The glycine cleavage system is composed of four components that only loosely associate: the P protein (EC 1.4.4.2), the T protein (EC 2.1.2.10), the L protein (EC 1.8.1.4) and the lipoyl-bearing H protein [3]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 37257-08-2 References: 1. Okamura-Ikeda, J., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken liver T protein, a component of the glycine cleavage system. J. Biol. Chem. 257 (1982) 135–139. [PMID: 7053363] 2. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] 3. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [PMID: 15642479] [EC 2.1.2.10 created 1972, modified 2003, modified 2006]

*EC 2.3.1.11 Common name: thioethanolamine S-acetyltransferase Reaction: acetyl-CoA + 2-aminoethanethiol = CoA + S-(2-aminoethyl)thioacetate Other name(s): thioltransacetylase B; thioethanolamine acetyltransferase; acetyl-CoA:thioethanolamine S- acetyltransferase Systematic name: acetyl-CoA:2-aminoethanethiol S-acetyltransferase Comments: 2-Sulfanylethanol (2-mercaptoethanol) can act as a substrate [1]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 9029-93-0 References: 1. Brady, R.O. and Stadtman, E.R. Enzymatic thioltransacetylation. J. Biol. Chem. 211 (1954) 621– 629. [PMID: 13221570] 2. Gunsalus, I.C. Group transfer and acyl-generating functions of lipoic acid derivatives. In: McElroy, W.D. and Glass, B. (Eds), A Symposium on the Mechanism of Enzyme Action, Johns Hopkins Press, Baltimore, 1954, pp. 545–580. [EC 2.3.1.11 created 1961, modified 2006]

*EC 2.3.1.38 Common name: [acyl-carrier-protein] S-acetyltransferase Reaction: acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier-protein] Other name(s): acetyl coenzyme A-acyl-carrier-protein transacylase; [acyl-carrier-protein]acetyltransferase; [ACP]acetyltransferase; ACAT Systematic name: acetyl-CoA:[acyl-carrier-protein] S-acetyltransferase Comments: This enzyme, along with EC 2.3.1.39, [acyl-carrier-protein] S-malonyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. The substrate acetyl-CoA protects the enzyme against inhibition by N-ethylmaleimide or iodoacetamide [4]. This is one of the activities associated with β-ketoacyl-ACP synthase III (EC 2.3.1.180) [5]. Links to other databases: BRENDA, ERGO, EXPASY, GTD, IUBMB, KEGG, CAS registry number: 37257-16-2 References: 1. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269–311. [PMID: 4561013]

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2. Vance, D.E., Mituhashi, O. and Bloch, K. Purification and properties of the fatty acid synthetase from Mycobacterium phlei. J. Biol. Chem. 248 (1973) 2303–2309. [PMID: 4698221] 3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases. J. Biol. Chem. 241 (1966) 2326–2332. [PMID: 5330116] 4. Lowe, P.N. and Rhodes, S. Purification and characterization of [acyl-carrier-protein] acetyltransferase from Escherichia coli. Biochem. J. 250 (1988) 789–796. [PMID: 3291856] 5. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of the β-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem. 267 (1992) 6807–6814. [PMID: 1551888] 6. Rangan, V.S. and Smith, S. Alteration of the substrate specificity of the malonyl-CoA/acetyl- CoA:acyl carrier protein S- domain of the multifunctional by mutation of a single arginine residue. J. Biol. Chem. 272 (1997) 11975–11978. [PMID: 9115261] [EC 2.3.1.38 created 1972, modified 2006]

*EC 2.3.1.39 Common name: [acyl-carrier-protein] S-malonyltransferase Reaction: malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier-protein] Other name(s): malonyl coenzyme A-acyl carrier protein transacylase; malonyl transacylase; malonyl transferase; malonyl-CoA-acyl carrier protein transacylase; [acyl carrier protein]malonyltransferase; MAT; FabD; malonyl-CoA:acyl carrier protein transacylase; malonyl-CoA:ACP transacylase; MCAT; malonyl- CoA:AcpM transacylase Systematic name: malonyl-CoA:[acyl-carrier-protein] S-malonyltransferase Comments: This enzyme, along with EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for polyketide biosynthesis [7]. The product of the reaction, malonyl-ACP, is an elongation substrate in fatty-acid biosynthesis. In Mycobacterium tuberculosis, holo-ACP (the product of EC 2.7.8.7, holo- [acyl-carrier-protein] synthase) is the preferred substrate [5]. Links to other databases: BRENDA, ERGO, EXPASY, GTD, IUBMB, KEGG, PDB, CAS registry number: 37257-17-3 References: 1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase. Methods Enzymol. 14 (1969) 50–53. 2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269–311. [PMID: 4561013] 3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases. J. Biol. Chem. 241 (1966) 2326–2332. [PMID: 5330116] 4. Joshi, V.C. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XXVI. Purification and properties of malonyl-coenzyme A--acyl carrier protein transacylase of Escherichia coli. Arch. Biochem. Biophys. 143 (1971) 493–505. [PMID: 4934182] 5. Kremer, L., Nampoothiri, K.M., Lesjean, S., Dover, L.G., Graham, S., Betts, J., Brennan, P.J., Minnikin, D.E., Locht, C. and Besra, G.S. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J. Biol. Chem. 276 (2001) 27967–27974. [PMID: 11373295] 6. Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J., O'Connell, J.D., 3rd, Khosla, C. and Stroud, R.M. , specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11 (2003) 147–154. [PMID: 12575934] 7. Szafranska, A.E., Hitchman, T.S., Cox, R.J., Crosby, J. and Simpson, T.J. Kinetic and mechanistic analysis of the malonyl CoA:ACP transacylase from Streptomyces coelicolor indicates a single catalytically competent serine nucleophile at the . Biochemistry 41 (2002) 1421–1427. [PMID: 11814333] [EC 2.3.1.39 created 1972, modified 2006]

*EC 2.3.1.41 Common name: β-ketoacyl-acyl-carrier-protein synthase I Reaction: an acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = a 3-oxoacyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein] Glossary: an acyl-[acyl-carrier-protein] = R-CO-[acyl-carrier-protein] malonyl-[acyl-carrier-protein] = HOOC-CH2-CO-[acyl-carrier-protein] a 3-oxoacyl-[acyl-carrier-protein] = R-CO-CH2-CO-[acyl-carrier-protein] http://www.enzyme-database.org/newenz.php?sp=off Page 16 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Other name(s): β-ketoacyl-ACP synthase I; β-ketoacyl synthetase; β-ketoacyl-ACP synthetase; β-ketoacyl-acyl carrier protein synthetase; β-ketoacyl-[acyl carrier protein] synthase; β-ketoacylsynthase; condensing enzyme; 3-ketoacyl-acyl carrier protein synthase; fatty acid condensing enzyme; acyl- malonyl(acyl-carrier-protein)-condensing enzyme; acyl-malonyl acyl carrier protein-condensing enzyme; β-ketoacyl acyl carrier protein synthase; 3-oxoacyl-[acyl-carrier-protein] synthase; 3- oxoacyl:ACP synthase I; KASI; KAS I; FabF1; FabB Systematic name: acyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating) Comments: This enzyme is responsible for the chain-elongation step of dissociated (type II) fatty-acid biosynthesis, i.e. the addition of two C atoms to the fatty-acid chain. Escherichia coli mutants that lack this enzyme are deficient in unsaturated fatty acids. The enzyme can use fatty acyl thioesters of ACP (C2 to C16) as substrates, as well as fatty acyl thioesters of Co-A (C4 to C16) [4]. The substrate specificity is very similar to that of EC 2.3.1.179, β-ketoacyl-ACP synthase II, with the 9 exception that the latter enzyme is far more active with palmitoleoyl-ACP (C16Δ ) as substrate, allowing the to regulate its fatty-acid composition with changes in temperature [4,5]. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 9077-10-5 References: 1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase. Methods Enzymol. 14 (1969) 50–53. 2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269–311. [PMID: 4561013] 3. Toomey, R.E. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVI. Preparation and general properties of acyl-malonyl acyl carrier protein-condensing enzyme from Escherichia coli. J. Biol. Chem. 241 (1966) 1159–1165. [PMID: 5327099] 4. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250 (1975) 5289–5294. [PMID: 237914] 5. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β- ketoacyl-acyl carrier protein synthases I and II of Escherichia coli. J. Biol. Chem. 255 (1980) 11949–11956. [PMID: 7002930] 6. Wang, H. and Cronan, J.E. Functional replacement of the FabA and FabB proteins of Escherichia coli fatty acid synthesis by Enterococcus faecalis FabZ and FabF homologues. J. Biol. Chem. 279 (2004) 34489–34495. [PMID: 15194690] 7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636. [EC 2.3.1.41 created 1972, modified 2006]

*EC 2.3.1.109 Common name: arginine N-succinyltransferase Reaction: succinyl-CoA + L-arginine = CoA + 2-N-succinyl-L-arginine For diagram of arginine catabolism, click here Other name(s): arginine succinyltransferase; AstA; arginine and ornithine N2-succinyltransferase; AOST; AST; succinyl-CoA:L-arginine N2-succinyltransferase Systematic name: succinyl-CoA:L-arginine 2-N-succinyltransferase Comments: Also acts on L-ornithine. This is the first enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N- succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.81 (succinylornithine transaminase), EC 1.2.1.71 (succinylglutamate-semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase) [2,6]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 99676-48-9 References: 1. Vander Wauven, C., Jann, A., Haas, D., Leisinger, T. and Stalon, V. N2-succinylornithine in ornithine catabolism of Pseudomonas aeruginosa. Arch. Microbiol. 150 (1988) 400–404. [PMID: 3144259] 2. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882–886. [PMID: 2865249] 3. Tricot, C., Vander Wauven, C., Wattiez, R., Falmagne, P. and Stalon, V. Purification and properties of a succinyltransferase from Pseudomonas aeruginosa specific for both arginine and ornithine. Eur. J. Biochem. 224 (1994) 853–861. [PMID: 7523119] 4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280–7290. [PMID: 9393691]

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5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278–4286. [PMID: 9696779] 6. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314–352. [PMID: 3534538] 7. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 51 (1987) 178 only. [EC 2.3.1.109 created 1989, modified 2006]

EC 2.3.1.177 Common name: biphenyl synthase

Reaction: 3 malonyl-CoA + benzoyl-CoA = 4 CoA + 3,5-dihydroxybiphenyl + 4 CO2 Other name(s): BIS Systematic name: malonyl-CoA:benzoyl-CoA malonyltransferase Comments: A polyketide synthase that is involved in the production of the phytoalexin aucuparin. 2- Hydroxybenzoyl-CoA can also act as substrate but it leads to the derailment product 2- hydroxybenzoyltriacetic acid lactone. This enzyme uses the same starter substrate as EC 2.3.1.151, . References: 1. Liu, B., Beuerle, T., Klundt, T. and Beerhues, L. Biphenyl synthase from yeast-extract-treated cell cultures of Sorbus aucuparia. Planta 218 (2004) 492–496. [PMID: 14595561] [EC 2.3.1.177 created 2006]

EC 2.3.1.178 Common name: diaminobutyrate acetyltransferase Reaction: acetyl-CoA + L-2,4-diaminobutanoate = CoA + 4-N-acetyl-L-2,4-diaminobutanoate For diagram of ectoine biosynthesis, click here Other name(s): L-2,4-diaminobutyrate acetyltransferase; L-2,4-diaminobutanoate acetyltransferase; EctA; diaminobutyric acid acetyltransferase; DABA acetyltransferase; 2,4-diaminobutanoate acetyltransferase; DAB acetyltransferase; DABAcT; acetyl-CoA:L-2,4-diaminobutanoate N4- acetyltransferase Systematic name: acetyl-CoA:L-2,4-diaminobutanoate 4-N-acetyltransferase Comments: Requires Na+ or K+ for maximal activity [3]. Ornithine, lysine, aspartate, and α-, β- and γ- aminobutanoate cannot act as substrates [3]. However, acetyl-CoA can be replaced by propanoyl- CoA, although the reaction proceeds more slowly [3]. Forms part of the ectoine-biosynthesis pathway, the other enzymes involved being EC 2.6.1.76, diaminobutyrate—2-oxoglutarate transaminase and EC 4.2.1.108, ectoine synthase. References: 1. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine. FEMS Microbiol. Lett. 71 (1990) 157–162. 2. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano, M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. J. Bacteriol. 181 (1999) 91–99. [PMID: 9864317] 3. Reshetnikov, A.S., Mustakhimov, I.I., Khmelenina, V.N. and Trotsenko, Y.A. Cloning, purification, and characterization of diaminobutyrate acetyltransferase from the halotolerant methanotroph Methylomicrobium alcaliphilum 20Z. Biochemistry (Mosc.) 70 (2005) 878–883. [PMID: 16212543] 4. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl. Environ. Microbiol. 68 (2002) 772–783. [PMID: 11823218] 5. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. Microbiology 143 (1997) 1141–1149. [PMID: 9141677] [EC 2.3.1.178 created 2006]

EC 2.3.1.179 Common name: β-ketoacyl-acyl-carrier-protein synthase II Reaction: (Z)-hexadec-11-enoyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = (Z)-3-oxooctadec-13-

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enoyl-[acyl-carrier-protein] + CO2 +[acyl-carrier-protein] For diagram of reaction, click here Glossary: (Z)-hexadec-11-enoy-[acyl-carrier-protein] = palmitoleoyl-[acyl-carrier-protein] (Z)-3-oxooctadec-13-enoyl-[acyl-carrier-protein] = 3-oxovaccenoyl-[acyl-carrier-protein] Other name(s): KASII; KAS II; FabF; 3-oxoacyl-acyl carrier protein synthase I; β-ketoacyl-ACP synthase II Systematic name: (Z)-hexadec-11-enoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating) Comments: Involved in the dissociated (or type II) fatty acid biosynthesis system that occurs in plants and bacteria. While the substrate specificity of this enzyme is very similar to that of EC 2.3.1.41, β- ketoacyl-ACP synthase I, it differs in that palmitoleoyl-ACP is not a good substrate of EC 2.3.1.41 but is an excellent substrate of this enzyme [1,2]. The fatty-acid composition of Escherichia coli changes as a function of growth temperature, with the proportion of unsaturated fatty acids increasing with lower growth temperature. This enzyme controls the temperature-dependent regulation of fatty-acid composition, with mutants lacking this acivity being deficient in the elongation of palmitoleate to cis-vaccenate at low temperatures [3,4]. References: 1. D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250 (1975) 5289–5294. [PMID: 237914] 2. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β- ketoacyl-acyl carrier protein synthases I and II of Escherichia coli. J. Biol. Chem. 255 (1980) 11949–11956. [PMID: 7002930] 3. Price, A.C., Rock, C.O. and White, S.W. The 1.3-Angstrom-resolution crystal structure of β- ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae. J. Bacteriol. 185 (2003) 4136–4143. [PMID: 12837788] 4. Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr. β-Ketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis. J. Biol. Chem. 255 (1980) 3263–3265. [PMID: 6988423] 5. Magnuson, K., Carey, M.R. and Cronan, J.E., Jr. The putative fabJ gene of Escherichia coli fatty acid synthesis is the fabF gene. J. Bacteriol. 177 (1995) 3593–3595. [PMID: 7768872] 6. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636. [EC 2.3.1.179 created 2006]

EC 2.3.1.180 Common name: β-ketoacyl-acyl-carrier-protein synthase III

Reaction: acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier-protein] + CoA + CO2 Other name(s): 3-oxoacyl:ACP synthase III; 3-ketoacyl-acyl carrier protein synthase III; KASIII; KAS III; FabH; β- ketoacyl-acyl carrier protein synthase III; β-ketoacyl-ACP synthase III; β-ketoacyl (acyl carrier protein) synthase III Systematic name: acetyl-CoA:malonyl-[acyl-carrier-protein] C-acyltransferase Comments: Involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and bacteria. In contrast to EC 2.3.1.41 (β-ketoacyl-ACP synthase I) and EC 2.3.1.179 (β-ketoacyl- ACP synthase II), this enzyme specifically uses CoA thioesters rather than acyl-ACP as the primer [1]. In addition to the above reaction, the enzyme can also catalyse the reaction of EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, but to a much lesser extent [1]. The enzyme is responsible for initiating both straight- and branched-chain fatty-acid biosynthesis [2], with the substrate specificity in an organism reflecting the fatty-acid composition found in that organism [2,5]. For example, Streptococcus pneumoniae, a Gram-positive bacterium, is able to use both straight- and branched-chain (C4—C6) acyl-CoA primers [3] whereas Escherichia coli, a Gram- negative organism, uses primarily short straight-chain acyl CoAs, with a preference for acetyl-CoA [4,5]. References: 1. Tsay, J.T., Oh, W., Larson, T.J., Jackowski, S. and Rock, C.O. Isolation and characterization of the β-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem. 267 (1992) 6807–6814. [PMID: 1551888] 2. Han, L., Lobo, S. and Reynolds, K.A. Characterization of β-ketoacyl-acyl carrier protein synthase III from Streptomyces glaucescens and its role in initiation of fatty acid biosynthesis. J. Bacteriol. 180 (1998) 4481–4486. [PMID: 9721286] 3. Khandekar, S.S., Gentry, D.R., Van Aller, G.S., Warren, P., Xiang, H., Silverman, C., Doyle, M.L., Chambers, P.A., Konstantinidis, A.K., Brandt, M., Daines, R.A. and Lonsdale, J.T. Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae β-ketoacyl- acyl carrier protein synthase III (FabH). J. Biol. Chem. 276 (2001) 30024–30030. [PMID:

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11375394] 4. Choi, K.H., Kremer, L., Besra, G.S. and Rock, C.O. Identification and substrate specificity of β- ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem. 275 (2000) 28201–28207. [PMID: 10840036] 5. Qiu, X., Choudhry, A.E., Janson, C.A., Grooms, M., Daines, R.A., Lonsdale, J.T. and Khandekar, S.S. Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus. Protein Sci. 14 (2005) 2087–2094. [PMID: 15987898] 6. Li, Y., Florova, G. and Reynolds, K.A. Alteration of the fatty acid profile of Streptomyces coelicolor by replacement of the initiation enzyme 3-ketoacyl acyl carrier protein synthase III (FabH). J. Bacteriol. 187 (2005) 3795–3799. [PMID: 15901703] 7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636. [EC 2.3.1.180 created 2006]

EC 2.3.1.181 Common name: lipoyl(octanoyl) transferase Reaction: octanoyl-[acyl-carrier-protein] + protein = protein 6-N-(octanoyl)lysine + acyl carrier protein Glossary: lipoyl group Other name(s): LipB; lipoyl (octanoyl)-[acyl-carrier-protein]-protein N-lipoyltransferase; lipoyl (octanoyl)-acyl carrier protein:protein transferase; lipoate/octanoate transferase; lipoyltransferase; octanoyl-[acyl carrier protein]-protein N-octanoyltransferase; lipoyl(octanoyl)transferase Systematic name: octanoyl-[acyl-carrier-protein]:protein N-octanoyltransferase Comments: This is the first committed step in the biosynthesis of lipoyl cofactor. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2- oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,3]. Lipoyl-ACP can also act as a substrate [4] although octanoyl-ACP is likely to be the true substrate [6] . The other enzyme involved in the biosynthesis of lipoyl cofactor is EC 2.8.1.8, lipoyl synthase. An alternative lipoylation pathway involves EC 2.7.7.63, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues). References: 1. Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [PMID: 15642479] 2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411–6420. [PMID: 1655709] 3. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [PMID: 9218413] 4. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [PMID: 14700636] 5. Wada, M., Yasuno, R., Jordan, S.W., Cronan, J.E., Jr. and Wada, H. Lipoic acid metabolism in Arabidopsis thaliana: cloning and characterization of a cDNA encoding lipoyltransferase. Plant Cell Physiol. 42 (2001) 650–656. [PMID: 11427685] 6. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] [EC 2.3.1.181 created 2006]

*EC 2.4.1.195 Common name: N-hydroxythioamide S-β-glucosyltransferase Reaction: UDP- + N-hydroxy-2-phenylethanethioamide = UDP + desulfoglucotropeolin For diagram of glucotropeolin biosynthesis, click here Other name(s): desulfoglucosinolate-uridine diphosphate glucosyltransferase; uridine diphosphoglucose- thiohydroximate glucosyltransferase; thiohydroximate β-D-glucosyltransferase; UDPG:thiohydroximate glucosyltransferase; thiohydroximate S-glucosyltransferase; thiohydroximate http://www.enzyme-database.org/newenz.php?sp=off Page 20 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

glucosyltransferase; UDP-glucose:thiohydroximate S-β-D-glucosyltransferase Systematic name: UDP-glucose:N-hydroxy-2-phenylethanethioamide S-β-D-glucosyltransferase Comments: Involved with EC 2.8.2.24, desulfoglucosinolate , in the biosynthesis of thioglucosides in cruciferous plants. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 9068-14-8 References: 1. Jain, J.C., Reed, D.W., Groot Wassink, J.W.D. and Underhill, E.W. A radioassay of enzymes catalyzing the glucosylation and sulfation steps of glucosinolate biosynthesis in Brassica species. Anal. Biochem. 178 (1989) 137–140. [PMID: 2524977] 2. Reed, D.W., Davin, L., Jain, J.C., Deluca, V., Nelson, L. and Underhill, E.W. Purification and properties of UDP-glucose:thiohydroximate glucosyltransferase from Brassica napus L. seedlings. Arch. Biochem. Biophys. 305 (1993) 526–532. [PMID: 8373190] 3. Fahey, J.W., Zalcmann, A.T. and Talalay, P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56 (2001) 5–51. [PMID: 11198818] 4. Grubb, C.D., Zipp, B.J., Ludwig-Müller, J., Masuno, M.N., Molinski, T.F. and Abel, S. Arabidopsis glucosyltransferase UGT74B1 functions in glucosinolate biosynthesis and auxin homeostasis. Plant J. 40 (2004) 893–908. [EC 2.4.1.195 created 1992, modified 2006]

EC 2.4.1.243 Common name: 6G-fructosyltransferase

Reaction: [1-β-D-fructofuranosyl-(2→1)-]m+1 α-D-glucopyranoside + [1-β-D-fructofuranosyl-(2→1)-]n+1 α-D- glucopyranoside = [1-β-D-fructofuranosyl-(2→1)-]m α-D-glucopyranoside + [1-β-D-fructofuranosyl- (2→1)-]n+1 β-D-fructofuranosyl-(2→6)-α-D-glucopyranoside (m > 0; n ≥ 0) G F F Other name(s): fructan:fructan 6 -fructosyltransferase; 1 (1-β-D-fructofuranosyl)m :1 (1-β-D- G G G G fructofuranosyl)nsucrose 6 -fructosyltransferase; 6 -FFT; 6 -FT; 6 -fructotransferase Systematic name: 1F-oligo[β-D-fructofuranosyl-(2→1)-]sucrose 6G-β-D-fructotransferase Comments: This enzyme catalyses the transfer of the terminal (2→1)-linked β-D-fructosyl group of a mono- or oligosaccharide substituent on O-1 of the fructose residue of sucrose onto O-6 of its glucose residue [1]. For example, if 1-kestose [1F-(β-D-fructofuranosyl)sucrose] is both the donor and recipient in the reaction shown above, i.e., if m = 1 and n = 1, then the products will be sucrose and 6G-di-β-D-fructofuranosylsucrose. In this notation, the superscripts F and G are used to specify whether the fructose or glucose residue of the sucrose carries the substituent. Alternatively, this may be indicated by the presence and/or absence of primes (see http://www.chem.qmul.ac.uk/iupac/2carb/36.html#362). Sucrose cannot be a donor substrate in the reaction (i.e. m cannot be zero) and inulin cannot act as an acceptor. Side reactions catalysed are F transfer of a β-D-fructosyl group between compounds of the structure 1 -(1-β-D-fructofuranosyl)m- G 6 -(1-β-D-fructofuranosyl)n sucrose, where m ≥ 0 and n = 1 for the donor, and m ≥ 0 and n ≥ 0 for the acceptor. References: 1. Shiomi, N. Purification and characterisation of 6G-fructosyltransferase from the roots of asparagus (Asparagus officinalis L.). Carbohydr. Res. 96 (1981) 281–292. 2. Shiomi, N. Reverse reaction of fructosyl transfer catalysed by asparagus 6G-fructosyltransferase. Carbohydr. Res. 106 (1982) 166–169. 3. Shiomi, N. and Ueno, K. Cloning and expression of genes encoding fructosyltransferases from higher plants in food technology. J. Appl. Glycosci. 51 (2004) 177–183. 4. Ueno, K., Onodera, S., Kawakami, A., Yoshida, M. and Shiomi, N. Molecular characterization and expression of a cDNA encoding fructan:fructan 6G-fructosyltransferase from asparagus (Asparagus officinalis). New . 165 (2005) 813–824. [PMID: 15720693] [EC 2.4.1.243 created 2006]

EC 2.4.1.244 Common name: N-acetyl-β-glucosaminyl-glycoprotein 4-β-N-acetylgalactosaminyltransferase Reaction: UDP-N-acetyl-D-galactosamine + N-acetyl-β-D-glucosaminyl group = UDP + N-acetyl-β-D- galactosaminyl-(1→4)-N-acetyl-β-D-glucosaminyl group Glossary: N,N'-diacetyllactosediamine = N-acetyl-β-D-galactosaminyl-(1→4)-N-acetyl-D-glucosamine Other name(s): β1,4-N-acetylgalactosaminyltransferase III; β4GalNAc-T3; β1,4-N-acetylgalactosaminyltransferase IV; β4GalNAc-T4

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Systematic name: UDP-N-acetyl-D-galactosamine:N-acetyl-D-glucosaminyl-group β-1,4-N- acetylgalactosaminyltransferase Comments: The enzyme from human can transfer N-acetyl-D-galactosamine (GalNAc) to N-glycan and O- glycan substrates that have N-acetyl-D-glucosamine (GlcNAc) but not D-glucuronic acid (GlcUA) at their non-reducing end. The N-acetyl-β-D-glucosaminyl group is normally on a core oligosaccharide although benzyl glycosides have been used in enzyme-characterization experiments. Some glycohormones, e.g. lutropin and thyrotropin contain the N-glycan structure containing the N-acetyl- β-D-galactosaminyl-(1→4)-N-acetyl-β-D-glucosaminyl group. References: 1. Sato, T., Gotoh, M., Kiyohara, K., Kameyama, A., Kubota, T., Kikuchi, N., Ishizuka, Y., Iwasaki, H., Togayachi, A., Kudo, T., Ohkura, T., Nakanishi, H. and Narimatsu, H. Molecular cloning and characterization of a novel human β1,4-N-acetylgalactosaminyltransferase, β4GalNAc-T3, responsible for the synthesis of N,N'-diacetyllactosediamine, GalNAc β1-4GlcNAc. J. Biol. Chem. 278 (2003) 47534–47544. [PMID: 12966086] 2. Gotoh, M., Sato, T., Kiyohara, K., Kameyama, A., Kikuchi, N., Kwon, Y.D., Ishizuka, Y., Iwai, T., Nakanishi, H. and Narimatsu, H. Molecular cloning and characterization of β1,4-N- acetylgalactosaminyltransferases IV synthesizing N,N'-diacetyllactosediamine. FEBS Lett. 562 (2004) 134–140. [PMID: 15044014] [EC 2.4.1.244 created 2006]

*EC 2.6.1.52 Common name: phosphoserine transaminase Reaction: (1) O-phospho-L-serine + 2-oxoglutarate = 3-phosphonooxypyruvate + L-glutamate (2) 4-phosphonooxy-L-threonine + 2-oxoglutarate = (3R)-3-hydroxy-2-oxo-4- phosphonooxybutanoate + L-glutamate For diagram of reaction, click here, for mechanism, click here and for diagram of pyridoxal biosynthesis, click here Other name(s): PSAT; phosphoserine aminotransferase; 3-phosphoserine aminotransferase; hydroxypyruvic phosphate-glutamic transaminase; L-phosphoserine aminotransferase; phosphohydroxypyruvate transaminase; phosphohydroxypyruvic-glutamic transaminase; 3-O-phospho-L-serine:2- oxoglutarate aminotransferase; SerC; PdxC; 3PHP transaminase Systematic name: O-phospho-L-serine:2-oxoglutarate aminotransferase Comments: A pyridoxal-phosphate protein. This enzyme catalyses the second step in the phosphorylated pathway of serine biosynthesis in Escherichia coli [2,3]. It also catalyses the third step in the biosynthesis of the coenzyme pyridoxal 5′-phosphate in Escherichia coli (using Reaction 2 above) [3]. In Escherichia coli, pyridoxal 5′-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4- phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5′-phosphate as substrate). Pyridoxal phosphate is the cofactor for both activities and therefore seems to be involved in its own biosynthesis [4]. Non-phosphorylated forms of serine and threonine are not substrates [4]. Links to other databases: BRENDA, ERGO, EXPASY, GO, GTD, IUBMB, KEGG, PDB, CAS registry number: 9030-90-4 References: 1. Hirsch, H. and Greenberg, D.M. Studies on phosphoserine aminotransferase of sheep brain. J. Biol. Chem. 242 (1967) 2283–2287. [PMID: 6022873] 2. Pizer, L.I. The pathway and control of serine biosynthesis in Escherichia coli. J. Biol. Chem. 238 (1963) 3934–3944. [PMID: 14086727] 3. Zhao, G. and Winkler, M.E. A novel α-ketoglutarate reductase activity of the serA-encoded 3- phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible implications for human 2-hydroxyglutaric aciduria. J. Bacteriol. 178 (1996) 232–239. [PMID: 8550422] 4. Drewke, C., Klein, M., Clade, D., Arenz, A., Müller, R. and Leistner, E. 4-O-phosphoryl-L- threonine, a substrate of the pdxC(serC) gene product involved in vitamin B6 biosynthesis. FEBS Lett. 390 (1996) 179–182. [PMID: 8706854] 5. Zhao, G. and Winkler, M.E. 4-Phospho-hydroxy-L-threonine is an obligatory intermediate in pyridoxal 5′-phosphate coenzyme biosynthesis in Escherichia coli K-12. FEMS Microbiol. Lett. 135 (1996) 275–280. [PMID: 8595869] [EC 2.6.1.52 created 1972, modified 2006]

*EC 2.6.1.76 Common name: diaminobutyrate—2-oxoglutarate transaminase Reaction: L-2,4-diaminobutanoate + 2-oxoglutarate = L-aspartate 4-semialdehyde + L-glutamate http://www.enzyme-database.org/newenz.php?sp=off Page 22 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

For diagram of ectoine biosynthesis, click here Other name(s): L-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase; 2,4-diaminobutyrate 4-aminotransferase; diaminobutyrate aminotransferase; DABA aminotransferase; DAB aminotransferase; EctB; diaminibutyric acid aminotransferase; L-2,4-diaminobutyrate:2-oxoglutarate 4-aminotransferase Systematic name: L-2,4-diaminobutanoate:2-oxoglutarate 4-aminotransferase Comments: A pyridoxal-phosphate protein that requires potassium for activity [4]. In the proteobacterium Acinetobacter baumannii, this enzyme is a product of the ddc gene that also encodes EC 4.1.1.85, diaminobutyrate decarboxylase. Differs from EC 2.6.1.46, diaminobutyrate—pyruvate transaminase, which has pyruvate as the amino-group acceptor. This is the first enzyme in the ectoine- biosynthesis pathway, the other enzymes involved being EC 2.3.1.178, diaminobutyrate acetyltransferase and EC 4.2.1.108, ectoine synthase [3,4]. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, CAS registry number: 196622-96-5 References: 1. Ikai, H. and Yamamoto, S. Identification and analysis of a gene encoding L-2,4- diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production pathway in Acinetobacter baumannii. J. Bacteriol. 179 (1997) 5118–5125. [PMID: 9260954] 2. Ikai, H. and Yamamoto, S. Two genes involved in the 1,3-diaminopropane production pathway in Haemophilus influenzae. Biol. Pharm. Bull. 21 (1998) 170–173. [PMID: 9514614] 3. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine. FEMS Microbiol. Lett. 71 (1990) 157–162. 4. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano, M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. J. Bacteriol. 181 (1999) 91–99. [PMID: 9864317] 5. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl. Environ. Microbiol. 68 (2002) 772–783. [PMID: 11823218] 6. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. Microbiology 143 (1997) 1141–1149. [PMID: 9141677] [EC 2.6.1.76 created 2000, modified 2006]

EC 2.6.1.81 Common name: succinylornithine transaminase Reaction: 2-N-succinyl-L-ornithine + 2-oxoglutarate = N-succinyl-L-glutamate 5-semialdehyde + L-glutamate For diagram of arginine catabolism, click here Other name(s): succinylornithine aminotransferase; N2-succinylornithine 5-aminotransferase; AstC; SOAT; N2- succinyl-L-ornithine:2-oxoglutarate 5-aminotransferase Systematic name: 2-N-succinyl-L-ornithine:2-oxoglutarate 5-aminotransferase Comments: A pyridoxal-phosphate protein. Also acts on 2-N-acetyl-L-ornithine and L-ornithine, but more slowly [3]. In Pseudomonas aeruginosa, the arginine-inducible succinylornithine transaminase, acetylornithine transaminase (EC 2.6.1.11) and ornithine aminotransferase (EC 2.6.1.13) activities are catalysed by the same enzyme, but this is not the case in all species [5]. This is the third enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.81 (succinylornithine transaminase), EC 1.2.1.71 (succinylglutamate- semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase) [3, 6]. References: 1. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882–886. [PMID: 2865249] 2. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278–4286. [PMID: 9696779] 3. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314–352. [PMID: 3534538] 4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280–7290. [PMID: 9393691] 5. Stalon, V., Vander Wauven, C., Momin, P. and Legrain, C. Catabolism of arginine, citrulline and ornithine by Pseudomonas and related bacteria. J. Gen. Microbiol. 133 (1987) 2487–2495.

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[PMID: 3129535] [EC 2.6.1.81 created 2006]

EC 2.6.99.2 Common name: pyridoxine 5′-phosphate synthase Reaction: 1-deoxy-D-xylulose 5-phosphate + 3-amino-2-oxopropyl phosphate = pyridoxine 5′-phosphate + phosphate + 2 H2O For diagram of pyridoxal biosynthesis, click here Other name(s): pyridoxine 5-phosphate phospho lyase; PNP synthase; PdxJ Systematic name: 1-deoxy-D-xylulose-5-phosphate:3-amino-2-oxopropyl phosphate 3-amino-2-oxopropyltransferase (phosphate-hydrolysing; cyclizing) Comments: In Escherichia coli, the coenzyme pyridoxal 5′-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4- phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4- hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5′-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5′-phosphate as substrate). 1-Deoxy-D-xylulose cannot replace 1- deoxy-D-xylulose 5-phosphate as a substrate [3].

References: 1. Garrido-Franco, M. Pyridoxine 5′-phosphate synthase: de novo synthesis of vitamin B6 and beyond. Biochim. Biophys. Acta 1647 (2003) 92–97. [PMID: 12686115] 2. Garrido-Franco, M., Laber, B., Huber, R. and Clausen, T. Enzyme-ligand complexes of pyridoxine 5′-phosphate synthase: implications for substrate binding and catalysis. J. Mol. Biol. 321 (2002) 601–612. [PMID: 12206776] 3. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B6 biosynthesis: formation of pyridoxine 5′-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D- xylulose-5-phosphate by PdxA and PdxJ protein. FEBS Lett. 449 (1999) 45–48. [PMID: 10225425] 4. Franco, M.G., Laber, B., Huber, R. and Clausen, T. Structural basis for the function of pyridoxine 5′-phosphate synthase. Structure 9 (2001) 245–253. [PMID: 11286891] [EC 2.6.99.2 created 2006]

*EC 2.7.1.151 Common name: inositol-polyphosphate multikinase Reaction: (1) ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate (2) ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate = ADP + 1D-myo-inositol 1,3,4,5,6- pentakisphosphate For diagram of myo-inositol-phosphate metabolism, click here Other name(s): IpK2; IP3/IP4 6-/3-kinase; IP3/IP4 dual-specificity 6-/3-kinase; IpmK; ArgRIII; AtIpk2α; AtIpk2β; inositol polyphosphate 6-/3-/5-kinase Systematic name: ATP:1D-myo-inositol-1,4,5-trisphosphate 6-phosphotransferase

Comments: This enzyme also phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4, Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5, and Ins(1,3,4,5,6)P4 to Ins(PP)P4, isomer unknown. The enzyme from the plant Arabidopsis thaliana can also phosphorylate Ins(1,3,4,6)P4 and Ins(1,2,3,4,6)P5 at the D-5-position to produce 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate (InsP6), respectively [3]. Yeast produce InsP6 from Ins(1,4,5)P3 by the actions of this enzyme and EC 2.7.1.158, inositol- pentakisphosphate 2-kinase [4]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG References: 1. Saiardi, A., Erdjument-Bromage, H., Snowman, A.M., Tempst, P. and Snyder, S.H. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr. Biol. 9 (1999) 1323–1326. [PMID: 10574768] 2. Odom, A.R., Stahlberg, A., Wente, S.R. and York, J.D. A role for nuclear inositol 1,4,5- trisphosphate kinase in transcriptional control. Science 287 (2000) 2026–2029. [PMID: 10720331] 3. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J. Biol. Chem. 277 (2002) 42711–42718. [PMID: 12226109] 4. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the production of inositol hexakisphosphate in human cells. J. Biol. Chem. 280 (2005) 1911–1920. [PMID: 15531582] http://www.enzyme-database.org/newenz.php?sp=off Page 24 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

[EC 2.7.1.151 created 2002, modified 2006]

EC 2.7.1.158 Common name: inositol-pentakisphosphate 2-kinase Reaction: ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol hexakisphosphate Other name(s): IP5 2-kinase; Gsl1p; Ipk1p; inositol ; inositol 1,3,4,5,6-pentakisphosphate 2- kinase; Ins(1,3,4,5,6)P5 2-kinase Systematic name: ATP:1D-myo-inositol 1,3,4,5,6-pentakisphosphate 2-phosphotransferase

Comments: The enzyme can also use Ins(1,4,5,6)P4 [2] and Ins(1,4,5)P3 [3] as substrate. Inositol hexakisphosphate (phytate) accumulates in storage protein bodies during seed development and, when hydrolysed, releases stored nutrients to the developing seedling before the plant is capable of absorbing nutrients from its environment [5]. References: 1. York, J.D., Odom, A.R., Murphy, R., Ives, E.B. and Wente, S.R. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 285 (1999) 96–100. [PMID: 10390371] 2. Phillippy, B.Q., Ullah, A.H. and Ehrlich, K.C. Purification and some properties of inositol 1,3,4,5,6-Pentakisphosphate 2-kinase from immature soybean seeds. J. Biol. Chem. 269 (1994) 28393–28399. [PMID: 7961779] 3. Phillippy, B.Q., Ullah, A.H. and Ehrlich, K.C. Additions and corrections to Purification and some properties of inositol 1,3,4,5,6-pentakisphosphate 2-kinase from immature soybean seeds. J. Biol. Chem. 270 (1997) 7782 only. 4. Ongusaha, P.P., Hughes, P.J., Davey, J. and Michell, R.H. Inositol hexakisphosphate in Schizosaccharomyces pombe: synthesis from Ins(1,4,5)P3 and osmotic regulation. Biochem. J. 335 (1998) 671–679. [PMID: 9794810] 5. Miller, A.L., Suntharalingam, M., Johnson, S.L., Audhya, A., Emr, S.D. and Wente, S.R. Cytoplasmic inositol hexakisphosphate production is sufficient for mediating the Gle1-mRNA export pathway. J. Biol. Chem. 279 (2004) 51022–51032. [PMID: 15459192] 6. Stevenson-Paulik, J., Odom, A.R. and York, J.D. Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J. Biol. Chem. 277 (2002) 42711–42718. [PMID: 12226109] [EC 2.7.1.158 created 2006]

EC 2.7.1.159 Common name: inositol-1,3,4-trisphosphate 5/6-kinase Reaction: (1) ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate (2) ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate

Other name(s): Ins(1,3,4)P3 5/6-kinase; inositol trisphosphate 5/6-kinase Systematic name: ATP:1D-myo-inositol 1,3,4-trisphosphate 5-phosphotransferase Comments: In humans, this enzyme, along with EC 2.7.1.127 (inositol-trisphosphate 3-kinase), EC 2.7.1.140 (inositol-tetrakisphosphate 5-kinase) and EC 2.7.1.158 (inositol pentakisphosphate 2-kinase) is involved in the production of inositol hexakisphosphate (InsP6). InsP6 is involved in many cellular processes, including mRNA export from the nucleus [2]. Yeasts do not have this enzyme, so produce InsP6 from Ins(1,4,5)P3 by the actions of EC 2.7.1.151 (inositol-polyphosphate multikinase) and EC 2.7.1.158 (inositol-pentakisphosphate 2-kinase) [2]. References: 1. Wilson, M.P. and Majerus, P.W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme. J. Biol. Chem. 271 (1996) 11904–11910. [PMID: 8662638] 2. Verbsky, J.W., Chang, S.C., Wilson, M.P., Mochizuki, Y. and Majerus, P.W. The pathway for the production of inositol hexakisphosphate in human cells. J. Biol. Chem. 280 (2005) 1911–1920. [PMID: 15531582] 3. Miller, G.J., Wilson, M.P., Majerus, P.W. and Hurley, J.H. Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase. Mol. Cell. 18 (2005) 201–212. [PMID: 15837423] [EC 2.7.1.159 created 2006]

EC 2.7.4.22 Common name: UMP kinase http://www.enzyme-database.org/newenz.php?sp=off Page 25 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Reaction: ATP + UMP = ADP + UDP Other name(s): uridylate kinase; UMPK; uridine monophosphate kinase; PyrH; UMP-kinase; SmbA Systematic name: ATP:UMP phosphotransferase Comments: This enzyme is strictly specific for UMP as substrate and is used by prokaryotes in the de novo synthesis of pyrimidines, in contrast to eukaryotes, which use the dual-specificity enzyme UMP/CMP kinase (EC 2.7.4.14) for the same purpose [2]. This enzyme is the subject of feedback regulation, being inhibited by UTP and activated by GTP [1]. References: 1. Serina, L., Blondin, C., Krin, E., Sismeiro, O., Danchin, A., Sakamoto, H., Gilles, A.M. and Bârzu, O. Escherichia coli UMP-kinase, a member of the aspartokinase family, is a hexamer regulated by guanine nucleotides and UTP. Biochemistry 34 (1995) 5066–5074. [PMID: 7711027] 2. Marco-Marín, C., Gil-Ortiz, F. and Rubio, V. The crystal structure of Pyrococcus furiosus UMP kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide biosynthesis. J. Mol. Biol. 352 (2005) 438–454. [PMID: 16095620] [EC 2.7.4.22 created 2006]

EC 2.7.7.63 Common name: lipoate—protein ligase Reaction: (1) ATP + lipoate = diphosphate + lipoyl-AMP (2) lipoyl-AMP + apoprotein = protein 6-N-(lipoyl)lysine + AMP Other name(s): LplA; lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B Systematic name: ATP:lipoate adenylyltransferase Comments: Requires Mg2+. Both 6S- and 6R-lipoates can act as substrates but there is a preference for the naturally occurring R-form. Selenolipoate, i.e. 5-(1,2-diselenolan-3-yl)pentanoic acid, and 6- sulfanyloctanoate can also act as substrates, but more slowly [2]. This enzyme is responsible for lipoylation in the presence of exogenous lipoic acid [7]. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [6]. This enzyme attaches lipoic acid to the lipoyl domains of these proteins, converting apoproteins into holoproteins. It is likely that an alternative pathway, involving EC 2.3.1.181, lipoyl(octanoyl) transferase and EC 2.8.1.8, lipoyl synthase, is the normal route for lipoylation [7]. References: 1. Morris, T.W., Reed, K.E. and Cronan, J.E., Jr. Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. J. Biol. Chem. 269 (1994) 16091–16100. [PMID: 8206909] 2. Green, D.E., Morris, T.W., Green, J., Cronan, J.E., Jr. and Guest, J.R. Purification and properties of the lipoate protein ligase of Escherichia coli. Biochem. J. 309 (1995) 853–862. [PMID: 7639702] 3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [PMID: 14700636] 4. Kim do, J., Kim, K.H., Lee, H.H., Lee, S.J., Ha, J.Y., Yoon, H.J. and Suh, S.W. Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains. J. Biol. Chem. 280 (2005) 38081–38089. [PMID: 16141198] 5. Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A. and Taniguchi, H. Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-. J. Biol. Chem. 280 (2005) 33645–33651. [PMID: 16043486] 6. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [PMID: 9218413] 7. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] [EC 2.7.7.63 created 2006]

*EC 2.8.1.6 Common name: biotin synthase Reaction: dethiobiotin + sulfur + 2 S-adenosyl-L-methionine = biotin + 2 L-methionine + 2 5′-deoxyadenosine Systematic name: dethiobiotin:sulfur Comments: This single-turnover enzyme is a member of the 'AdoMet radical ' (radical SAM) family, all members

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of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet [i.e. S- adenosylmethionine, or S-5′-deoxyadenosin-5′-yl)methionine], by the addition of an electron from an iron-sulfur centre. The enzyme has both a [2Fe-2S] and a [4Fe-4S] centre, and the latter is believed to donate the electron. Two molecules of AdoMet are converted into radicals; these activate positions 6 and 9 of dethiobiotin by abstracting a hydrogen atom from each, and thereby forming 5′-deoxyadenosine. Sulfur insertion into dethiobiotin at C-6 takes place with retention of configuration [3]. The sulfur donor has not been identified to date — it is neither elemental sulfur nor from AdoMet, but it may be from the [2Fe-2S] centre [4]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB References: 1. Shiuan, D. and Campbell, A. Transcriptional regulation and gene arrangement of Escherichia coli, Citrobacter freundii and Salmonella typhimurium biotin operons. Gene 67 (1988) 203–211. [PMID: 2971595] 2. Zhang, S., Sanyal, I., Bulboaca, G.H., Rich, A. and Flint, D.H. The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase. Arch. Biochem. Biophys. 309 (1994) 29–35. [PMID: 8117110] 3. Trainor, D.A., Parry, R.J. and Gitterman, A. Biotin biosynthesis. 2. Stereochemistry of sulfur introduction at C-4 of dethiobiotin. J. Am. Chem. Soc. 102 (1980) 1467–1468. 4. Lotierzo, M., Tse Sum Bui, B., Florentin, D., Escalettes, F. and Marquet, A. Biotin synthase mechanism: an overview. Biochem. Soc. Trans. 33 (2005) 820–823. [PMID: 16042606] 5. Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T. and Drennan, C.L. Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical enzyme. Science 303 (2004) 76–79. [PMID: 14704425] 6. Ugulava, N.B., Gibney, B.R. and Jarrett, J.T. Biotin synthase contains two distinct iron-sulfur cluster binding sites: chemical and spectroelectrochemical analysis of iron-sulfur cluster interconversions. Biochemistry 40 (2001) 8343–8351. [PMID: 11444981] [EC 2.8.1.6 created 1999, modified 2006]

EC 2.8.1.8 Common name: lipoyl synthase Reaction: protein 6-N-(octanoyl)lysine + 2 sulfur + 2 S-adenosyl-L-methionine = protein 6-N-(lipoyl)lysine + 2 L-methionine + 2 5′-deoxyadenosine Other name(s): LS; LipA; lipoate synthase Systematic name: protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase Comments: This enzyme is a member of the 'AdoMet radical' (radical SAM) family, all members of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet [i.e. S- adenosylmethionine, or S-(5′-deoxyadenosin-5′-yl)methionine], by the addition of an electron from an iron-sulfur centre. The radical is converted into 5′-deoxyadenosine when it abstracts a hydrogen atom from C-6 and C-8, leaving reactive radicals at these positions so that they can add sulfur, with inversion of configuration [4]. This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, with the other enzyme involved being EC 2.3.1.181, lipoyl(octanoyl) transferase. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,5]. An alternative lipoylation pathway involves EC 2.7.7.63, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) [7]. References: 1. Cicchillo, R.M. and Booker, S.J. Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide. J. Am. Chem. Soc. 127 (2005) 2860–2861. [PMID: 15740115] 2. Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411–6420. [PMID: 1655709] 3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [PMID: 14700636] 4. Cicchillo, R.M., Iwig, D.F., Jones, A.D., Nesbitt, N.M., Baleanu-Gogonea, C., Souder, M.G., Tu, L. and Booker, S.J. Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid. Biochemistry 43 (2004) 6378–6386. [PMID: 15157071] 5. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [PMID: 9218413] 6. Miller, J.R., Busby, R.W., Jordan, S.W., Cheek, J., Henshaw, T.F., Ashley, G.W., Broderick, J.B., http://www.enzyme-database.org/newenz.php?sp=off Page 27 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Cronan, J.E., Jr. and Marletta, M.A. Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein. Biochemistry 39 (2000) 15166–15178. [PMID: 11106496] 7. Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [PMID: 10966480] [EC 2.8.1.8 created 2006]

EC 3.1.3.76 Common name: lipid-phosphate phosphatase

Reaction: (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)-9,10- dihydroxyoctadecanoate + phosphate Other name(s): hydroxy fatty ; dihydroxy fatty acid phosphatase; hydroxy lipid phosphatase; sEH (ambiguous); soluble epoxide hydrolase (ambiguous) Systematic name: (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate phosphohydrolase Comments: Requires Mg2+ for maximal activity. The enzyme from mammals is a bifunctional enzyme: the N- terminal domain exhibits lipid-phosphate-phosphatase activity and the C-terminal domain has the activity of EC 3.3.2.10, soluble epoxide hydrolase (sEH) [1]. The best substrates for this enzyme are 10-hydroxy-9-(phosphonooxy)octadecanoates, with the threo- form being a better substrate than the erythro- form [1]. The phosphatase activity is not found in plant sEH or in EC 3.3.2.9, microsomal epoxide hydrolase, from mammals [1]. References: 1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc. Natl. Acad. Sci. USA 100 (2003) 1558–1563. [PMID: 12574510] 2. Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA 100 (2003) 1552–1557. [PMID: 12574508] 3. Morisseau, C. and Hammock, B.D. Epoxide : mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [PMID: 15822179] 4. Tran, K.L., Aronov, P.A., Tanaka, H., Newman, J.W., Hammock, B.D. and Morisseau, C. Lipid sulfates and sulfonates are allosteric competitive inhibitors of the N-terminal phosphatase activity of the mammalian soluble epoxide hydrolase. Biochemistry 44 (2005) 12179–12187. [PMID: 16142916] 5. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] 6. Srivastava, P.K., Sharma, V.K., Kalonia, D.S. and Grant, D.F. Polymorphisms in human soluble epoxide hydrolase: effects on enzyme activity, enzyme stability, and quaternary structure. Arch. Biochem. Biophys. 427 (2004) 164–169. [PMID: 15196990] 7. Gomez, G.A., Morisseau, C., Hammock, B.D. and Christianson, D.W. Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry 43 (2004) 4716–4723. [PMID: 15096040] [EC 3.1.3.76 created 2006]

EC 3.1.13.5 Common name: ribonuclease D Reaction: Exonucleolytic cleavage that removes extra residues from the 3′-terminus of tRNA to produce 5′- mononucleotides Other name(s): RNase D Comments: Requires divalent cations for activity (Mg2+, Mn2+ or Co2+). Alteration of the 3′-terminal base has no effect on the rate of hydrolysis whereas modification of the 3′-terminal has a major effect. tRNA terminating with a 3′-phosphate is completely inactive [3]. This enzyme can convert a tRNA precursor into a mature tRNA [2]. References: 1. Ghosh, R.K. and Deutscher, M.P. Identification of an Escherichia coli nuclease acting on structurally altered transfer RNA molecules. J. Biol. Chem. 253 (1978) 997–1000. [PMID: 342522] 2. Cudny, H., Zaniewski, R. and Deutscher, M.P. Escherichia coli RNase D. Purification and structural characterization of a putative processing nuclease. J. Biol. Chem. 256 (1981) 5627– 5632. [PMID: 6263885] 3. Cudny, H., Zaniewski, R. and Deutscher, M.P. Escherichia coli RNase D. Catalytic properties and substrate specificity. J. Biol. Chem. 256 (1981) 5633–5637. [PMID: 6263886] 4. Zhang, J.R. and Deutscher, M.P. Cloning, characterization, and effects of overexpression of the http://www.enzyme-database.org/newenz.php?sp=off Page 28 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Escherichia coli rnd gene encoding RNase D. J. Bacteriol. 170 (1988) 522–527. [PMID: 2828310] [EC 3.1.13.5 created 2006]

*EC 3.1.26.3 Common name: ribonuclease III Reaction: Endonucleolytic cleavage to a 5′-phosphomonoester Other name(s): RNase III; ribonuclease 3 Comments: This is an endoribonuclease that cleaves double-stranded RNA molecules [4]. The cleavage can be either a single-stranded nick or double-stranded break in the RNA, depending in part upon the degree of base-pairing in the region of the cleavage site [5]. Specificity is conferred by negative determinants, i.e., the presence of certain Watson-Crick base-pairs at specific positions that strongly inhibit cleavage [6]. RNase III is involved in both rRNA processing and mRNA processing and decay. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 78413-14-6 References: 1. Crouch, R.J. Ribonuclease 3 does not degrade deoxyribonucleic acid-ribonucleic acid hybrids. J. Biol. Chem. 249 (1974) 1314–1316. [PMID: 4592261] 2. Rech, J., Cathala, G. and Jeanteur, P. Isolation and characterization of a ribonuclease activity specific for double-stranded RNA (RNase D) from Krebs II ascites cells. J. Biol. Chem. 255 (1980) 6700–6706. [PMID: 6248530] 3. Robertson, H.D., Webster, R.E. and Zinder, N.D. Purification and properties of ribonuclease III from Escherichia coli. J. Biol. Chem. 243 (1968) 82–91. [PMID: 4865702] 4. Grunberg-Manago, M. Messenger RNA stability and its role in control of gene expression in bacteria and phages. Annu. Rev. Genet. 33 (1999) 193–227. [PMID: 10690408] 5. Court, D. RNA processing and degradation by RNase III in control of mRNA stability. In: Belasco, J.G. and Brawerman, G. (Eds), Control of Messenger RNA Stability, Academic Press, New York, 1993, pp. 71–116. 6. Zhang, K. and Nicholson, A.W. Regulation of ribonuclease III processing by double-helical sequence antideterminants. Proc. Natl. Acad. Sci. USA 94 (1997) 13437–13441. [PMID: 9391043] [EC 3.1.26.3 created 1978, modified 2006]

*EC 3.2.1.81 Common name: β-agarase Reaction: Hydrolysis of 1,4-β-D-galactosidic linkages in agarose, giving the tetramer as the predominant product Glossary: agarose = a polysaccharide In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate residues are 3,6-anhydro , the prefix 'neo' designates an oligosaccharide whose non- reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example: neoagarobiose = 3,6-anhydro-α-L-galactopyranosyl-(1→3)-D- agarobiose = β-D- galactopyranosyl-(1→4)-3,6-anhydro-L-galactose Other name(s): agarase (ambiguous); AgaA; AgaB; endo-β-agarase; agarose 3-glycanohydrolase (incorrect) Systematic name: agarose 4-glycanohydrolase Comments: Also acts on porphyran, but more slowly [1]. This enzyme cleaves the β-(1→4) linkages of agarose in a random manner with retention of the anomeric-bond configuration, producing β-anomers that give rise progressively to α-anomers when mutarotation takes place [6]. The end products of hydrolysis are neoagarotetraose and neoagarohexaose in the case of AgaA from the marine bacterium Zobellia galactanivorans, and neoagarotetraose and neoagarobiose in the case of AgaB [6]. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 37288-57-6 References: 1. Duckworth, M. and Turvey, J.R. The action of a bacterial agarase on agarose, porphyran and alkali-treated porphyran. Biochem. J. 113 (1969) 687–692. [PMID: 5386190] 2. Allouch, J., Jam, M., Helbert, W., Barbeyron, T., Kloareg, B., Henrissat, B. and Czjzek, M. The three-dimensional structures of two β-agarases. J. Biol. Chem. 278 (2003) 47171–47180. [PMID: 12970344] 3. Ohta, Y., Nogi, Y., Miyazaki, M., Li, Z., Hatada, Y., Ito, S. and Horikoshi, K. Enzymatic properties and nucleotide and amino acid sequences of a thermostable β-agarase from the novel marine isolate, JAMB-A94. Biosci. Biotechnol. Biochem. 68 (2004) 1073–1081. [PMID: 15170112]

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4. Ohta, Y., Hatada, Y., Nogi, Y., Miyazaki, M., Li, Z., Akita, M., Hidaka, Y., Goda, S., Ito, S. and Horikoshi, K. Enzymatic properties and nucleotide and amino acid sequences of a thermostable β-agarase from a novel species of deep-sea Microbulbifer. Appl. Microbiol. Biotechnol. 64 (2004) 505–514. [PMID: 15088129] 5. Sugano, Y., Terada, I., Arita, M., Noma, M. and Matsumoto, T. Purification and characterization of a new agarase from a marine bacterium, Vibrio sp. strain JT0107. Appl. Environ. Microbiol. 59 (1993) 1549–1554. [PMID: 8517750] 6. Jam, M., Flament, D., Allouch, J., Potin, P., Thion, L., Kloareg, B., Czjzek, M., Helbert, W., Michel, G. and Barbeyron, T. The endo-β-agarases AgaA and AgaB from the marine bacterium Zobellia galactanivorans: two paralogue enzymes with different molecular organizations and catalytic behaviours. Biochem. J. 385 (2005) 703–713. [PMID: 15456406] [EC 3.2.1.81 created 1972, modified 2006]

*EC 3.2.1.83 Common name: κ-carrageenase Reaction: Endohydrolysis of 1,4-β-D-linkages between D-galactose 4-sulfate and 3,6-anhydro-D-galactose in κ-carrageenans For diagram of reaction, click here Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non- reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example: ι-neocarrabiose = 3,6-anhydro-2-O-sulfo-α-D-galactopyranosyl-(1→3)-4-O-sulfo-D-galactose ι-carrabiose = 4-O-sulfo- β-D-galactopyranosyl-(1→4)-3,6-anhydro-2-O-sulfo-D-galactose Other name(s): κ-carrageenan 4-β-D-glycanohydrolase Systematic name: κ-carrageenan 4-β-D-glycanohydrolase (configuration-retaining) Comments: The main products of hydrolysis are neocarrabiose-sulfate and neocarratetraose-sulfate [5]. Unlike EC 3.2.1.157 (ι-carrageenase), but similar to EC 3.2.1.81 (β-agarase), this enzyme proceeds with retention of the anomeric configuration. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 37288-59-8 References: 1. Weigl, J. and Yashe, W. The enzymic hydrolysis of carrageenan by Pseudomonas carrageenovora: purification of a κ-carrageenase. Can. J. Microbiol. 12 (1966) 939–947. [PMID: 5972647] 2. Potin, P., Sanseau, A., Le Gall, Y., Rochas, C. and Kloareg, B. Purification and characterization of a new κ-carrageenase from a marine Cytophaga-like bacterium. Eur. J. Biochem. 201 (1991) 241–247. [PMID: 1915370] 3. Potin, P., Richard, C., Barbeyron, T., Henrissat, B., Gey, C., Petillot, Y., Forest, E., Dideberg, O., Rochas, C. and Kloareg, B. Processing and hydrolytic mechanism of the cgkA-encoded κ- carrageenase of Alteromonas carrageenovora. Eur. J. Biochem. 228 (1995) 971–975. [PMID: 7737202] 4. Michel, G., Barbeyron, T., Flament, D., Vernet, T., Kloareg, B. and Dideberg, O. Expression, purification, crystallization and preliminary x-ray analysis of the κ-carrageenase from Pseudoalteromonas carrageenovora. Acta Crystallogr. D Biol. Crystallogr. 55 (1999) 918–920. [PMID: 10089334] 5. Michel, G., Chantalat, L., Duee, E., Barbeyron, T., Henrissat, B., Kloareg, B. and Dideberg, O. The κ-carrageenase of P. carrageenovora features a tunnel-shaped active site: a novel insight in the evolution of Clan-B glycoside hydrolases. Structure 9 (2001) 513–525. [PMID: 11435116] [EC 3.2.1.83 created 1972, modified 2006]

EC 3.2.1.155 Common name: xyloglucan-specific exo-β-1,4-glucanase

Reaction: xyloglucan + H2O = xyloglucan oligosaccharides (exohydrolysis of 1,4-β-D-glucosidic linkages in xyloglucan) Other name(s): Cel74A Systematic name: [(1→6)-α-D-xylo]-(1→4)-β-D-glucan exo-glucohydrolase Comments: The enzyme from Chrysosporium lucknowense is an endoglucanase, i.e. acquires the specificity of EC 3.2.1.151, xyloglucan-specific endo-β-1,4-glucanase, when it acts on linear substrates without bulky substituents on the polymeric backbone (e.g. carboxymethylcellulose). However, it switches to an exoglucanase mode of action when bulky side chains are present (as in the case of

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xyloglucan). The enzyme can also act on barley β-glucan, but more slowly. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG References: 1. Grishutin, S.G., Gusakov, A.V., Markov, A.V., Ustinov, B.B., Semenova, M.V. and Sinitsyn, A.P. Specific xyloglucanases as a new class of polysaccharide-degrading enzymes. Biochim. Biophys. Acta 1674 (2004) 268–281. [PMID: 15541296] [EC 3.2.1.155 created 2005, withdrawn at public-review stage, modified and reinstated 2006]

EC 3.2.1.157 Common name: ι-carrageenase Reaction: Endohydrolysis of 1,4-β-D-linkages between D-galactose 4-sulfate and 3,6-anhydro-D-galactose-2- sulfate in ι-carrageenans For diagram of reaction, click here Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non- reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example: ι-neocarrabiose = 3,6-anhydro-2-O-sulfo-α-D-galactopyranosyl-(1→3)-4-O-sulfo-D-galactose ι-carrabiose = 4-O-sulfo-β-D-galactopyranosyl-(1→4)-3,6-anhydro-2-O-sulfo-D-galactose Systematic name: ι-carrageenan 4-β-D-glycanohydrolase (configuration-inverting) Comments: The main products of hydrolysis are ι-neocarratetraose sulfate and ι-neocarrahexaose sulfate. ι- Neocarraoctaose is the shortest substrate oligomer that can be cleaved. Unlike EC 3.2.1.81, β- agarase and EC 3.2.1.83, κ-carrageenase, this enzyme proceeds with inversion of the anomeric configuration. ι-Carrageenan differs from κ-carrageenan by possessing a sulfo group on O-2 of the 3,6-anhydro-D-galactose residues, in addition to that present in the κ-compound on O-4 of the D- galactose residues. References: 1. Barbeyron, T., Michel, G., Potin, P., Henrissat, B. and Kloareg, B. ι-Carrageenases constitute a novel family of glycoside hydrolases, unrelated to that of κ-carrageenases. J. Biol. Chem. 275 (2000) 35499–35505. [PMID: 10934194] 2. Michel, G., Chantalat, L., Fanchon, E., Henrissat, B., Kloareg, B. and Dideberg, O. The ι- carrageenase of Alteromonas fortis. A β-helix fold-containing enzyme for the degradation of a highly polyanionic polysaccharide. J. Biol. Chem. 276 (2001) 40202–40209. [PMID: 11493601] 3. Michel, G., Helbert, W., Kahn, R., Dideberg, O. and Kloareg, B. The structural bases of the processive degradation of ι-carrageenan, a main cell wall polysaccharide of red algae. J. Mol. Biol. 334 (2003) 421–433. [PMID: 14623184] [EC 3.2.1.157 created 2006]

EC 3.2.1.158 Common name: α-agarase Reaction: Endohydrolysis of 1,3-α-L-galactosidic linkages in agarose, yielding agarotetraose as the major product Glossary: agarose = a polysaccharide In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non- reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example: neoagarobiose = 3,6-anhydro-α-L-galactopyranosyl-(1→3)-D-galactose agarobiose = β-D-galactopyranosyl-(1→4)-3,6-anhydro-L-galactose Other name(s): agarase (ambiguous); agaraseA33 Systematic name: agarose 3-glycanohydrolase Comments: Requires Ca2+. The enzyme from Thalassomonas sp. can use agarose, agarohexaose and neoagarohexaose as substrate. The products of agarohexaose hydrolysis are dimers and tetramers, with agarotetraose being the predominant product, whereas hydrolysis of neoagarohexaose gives rise to two types of trimer. While the enzyme can also hydrolyse the highly sulfated agarose porphyran very efficiently, it cannot hydrolyse the related compounds κ- carrageenan (see EC 3.2.1.83) and ι-carrageenan (see EC 3.2.1.157) [2]. See also EC 3.2.1.81, β- agarase. References: 1. Potin, P., Richard, C., Rochas, C. and Kloareg, B. Purification and characterization of the α- agarase from Alteromonas agarlyticus (Cataldi) comb. nov., strain GJ1B. Eur. J. Biochem. 214

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(1993) 599–607. [PMID: 8513809] 2. Ohta, Y., Hatada, Y., Miyazaki, M., Nogi, Y., Ito, S. and Horikoshi, K. Purification and characterization of a novel α-agarase from a Thalassomonas sp. Curr. Microbiol. 50 (2005) 212– 216. [PMID: 15902469] [EC 3.2.1.158 created 2006]

EC 3.2.1.159 Common name: α-neoagaro-oligosaccharide hydrolase Reaction: Hydrolysis of the 1,3-α-L-galactosidic linkages of neoagaro-oligosaccharides that are smaller than a hexamer, yielding 3,6-anhydro-L-galactose and D-galactose Glossary: In the field of oligosaccharides derived from agarose, carrageenans, etc., in which alternate residues are 3,6-anhydro sugars, the prefix 'neo' designates an oligosaccharide whose non- reducing end is the anhydro sugar, and the absence of this prefix means that it is not. For example: neoagarobiose = 3,6-anhydro-α-L-galactopyranosyl-(1→3)-D-galactose agarobiose = β-D-galactopyranosyl-(1→4)-3,6-anhydro-L-galactose Other name(s): α-neoagarooligosaccharide hydrolase; α-NAOS hydrolase Systematic name: α-neoagaro-oligosaccharide 3-glycohydrolase Comments: When neoagarohexaose is used as a substrate, the oligosaccharide is cleaved at the non-reducing end to produce 3,6-anhydro-L-galactose and agaropentaose, which is further hydrolysed to agarobiose and agarotriose. With neoagarotetraose as substrate, the products are predominantly agarotriose and 3,6-anhydro-L-galactose. In Vibrio sp. the actions of EC 3.2.1.81, β-agarase and EC 3.2.1.159 can be used to degrade agarose to 3,6-anhydro-L-galactose and D-galactose. References: 1. Sugano, Y., Kodama, H., Terada, I., Yamazaki, Y. and Noma, M. Purification and characterization of a novel enzyme, α-neoagarooligosaccharide hydrolase (α-NAOS hydrolase), from a marine bacterium, Vibrio sp. strain JT0107. J. Bacteriol. 176 (1994) 6812–6818. [PMID: 7961439] [EC 3.2.1.159 created 2006]

EC 3.2.1.161 Common name: β-apiosyl-β-glucosidase

Reaction: 7-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyloxy]isoflavonoid + H2O = a 7-hydroxyisoflavonoid + β-D-apiofuranosyl-(1→6)-D-glucose Other name(s): isoflavonoid-7-O-β[D-apiosyl-(1→6)-β-D-glucoside] ; isoflavonoid 7-O-β-apiosyl- glucoside β-glucosidase; furcatin hydrolase Systematic name: 7-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyloxy]isoflavonoid β-D-apiofuranosyl-(1→6)-D- glucohydrolase Comments: The enzyme from the tropical tree Dalbergia nigrescens Kurz belongs in glycosyl hydrolase family 1. The enzyme removes from the natural substrates dalpatein 7-O-β-D- apiofuranosyl-(1→6)-β-D-glucopyranoside and 7-hydroxy-2′,4′,5′,6-tetramethoxy-7-O-β-D- apiofuranosyl-(1→6)-β-D-glucopyranoside (dalnigrein 7-O-β-D-apiofuranosyl-(1→6)-β-D- glucopyranoside) although it can also remove a single glucose residue from isoflavonoid 7-O- glucosides [2]. Daidzin and genistin are also substrates. References: 1. Hosel, W. and Barz, W. β- from Cicer arietinum L. Purification and Properties of isoflavone-7-O-glucoside-specific β-glucosidases. Eur. J. Biochem. 57 (1975) 607–616. [PMID: 240725] 2. Chuankhayan, P., Hua, Y., Svasti, J., Sakdarat, S., Sullivan, P.A. and Ketudat Cairns, J.R. Purification of an isoflavonoid 7-O-β-apiosyl-glucoside β-glycosidase and its substrates from Dalbergia nigrescens Kurz. Phytochemistry 66 (2005) 1880–1889. [PMID: 16098548] 3. Ahn, Y.O., Mizutani, M., Saino, H. and Sakata, K. Furcatin hydrolase from Viburnum furcatum Blume is a novel -specific acuminosidase in glycosyl hydrolase family 1. J. Biol. Chem. 279 (2004) 23405–23414. [PMID: 14976214] [EC 3.2.1.161 created 2006]

EC 3.3.2.3 Transferred entry: epoxide hydrolase. Now known to comprise two enzymes, microsomal epoxide hydrolase (EC 3.3.2.9) and soluble epoxide hydrolase (EC 3.3.2.10). http://www.enzyme-database.org/newenz.php?sp=off Page 32 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

[EC 3.3.2.3 created 1978, modified 1999, deleted 2006]

*EC 3.3.2.6

Common name: leukotriene-A4 hydrolase

Reaction: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)- (5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Glossary: leukotriene A4 = (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate leukotriene B4 = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate

Other name(s): LTA4 hydrolase; LTA4H; leukotriene A4 hydrolase Systematic name: (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase Comments: This is a bifunctional zinc metalloprotease that displays both epoxide hydrolase and aminopeptidase activities [4,6]. It preferentially cleaves tripeptides at an arginyl bond, with dipeptides and tetrapeptides being poorer substrates [6] (see EC 3.4.11.6, ). It also converts leukotriene A4 into leukotriene B4, unlike EC 3.2.2.10, soluble epoxide hydrolase, which converts leukotriene A4 into 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid [3,4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [3]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 90119-07-6 References: 1. Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils. Biochim. Biophys. Acta 840 (1985) 43–50. [PMID: 3995081] 2. Minami, M., Ohno, S., Kawasaki, H., Rådmark, O., Samuelsson, B., Jörnvall, H., Shimizu, T., Seyama, Y. and Suzuki, K. Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase - complete primary structure of an enzyme involved in eicosanoid synthesis. J. Biol. Chem. 262 (1987) 13873–13876. [PMID: 3654641] 3. Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6- dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453] 4. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] 5. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734] 6. Orning, L., Gierse, J.K. and Fitzpatrick, F.A. The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity. J. Biol. Chem. 269 (1994) 11269– 11267. [PMID: 8157657] 7. Ohishi, N., Izumi, T., Minami, M., Kitamura, S., Seyama, Y., Ohkawa, S., Terao, S., Yotsumoto, H., Takaku, F. and Shimizu, T. Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers. J. Biol. Chem. 262 (1987) 10200–10205. [PMID: 3038871] [EC 3.3.2.6 created 1989, modified 2006]

*EC 3.3.2.7 Common name: hepoxilin-epoxide hydrolase

Reaction: (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate + H2O = (5Z,9E,14Z)- (8ξ,11ξ,12S)-8,11,12-trihydroxyicosa-5,9,14-trienoate

Glossary: hepoxilin A3 = (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate trioxilin A3 = (5Z,9E,14Z)-(8ξ,11ξ,12S)-8,11,12-trihydroxyicosa-5,9,14-trienoate

Other name(s): hepoxilin epoxide hydrolase; hepoxylin hydrolase; hepoxilin A3 hydrolase Systematic name: (5Z,9E,14Z)-(8ξ,11R,12S)-11,12-epoxy-8-hydroxyicosa-5,9,14-trienoate hydrolase

Comments: Converts hepoxilin A3 into trioxilin A3. Highly specific for the substrate, having only slight activity with other epoxides such as leukotriene A4 and styrene oxide [2]. Hepoxilin A3 is an hydroxy- epoxide derivative of arachidonic acid that is formed via the 12- pathway [2]. It is probable that this enzyme plays a modulatory role in inflammation, vascular physiology, systemic glucose metabolism and neurological function [4]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide

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hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [3]. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 122096-98-4

References: 1. Pace-Asciak, C.R. Formation and metabolism of hepoxilin A3 by the rat brain. Biochem. Biophys. Res. Commun. 151 (1988) 493–498. [PMID: 3348791] 2. Pace-Asciak, C.R. and Lee, W.-S. Purification of hepoxilin epoxide hydrolase from rat liver. J. Biol. Chem. 264 (1989) 9310–9313. [PMID: 2722835] 3. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734] 4. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] [EC 3.3.2.7 created 1992, modified 2006]

EC 3.3.2.9 Common name: microsomal epoxide hydrolase

Reaction: cis-stilbene oxide + H2O = (+)-(1R,2R)-1,2-diphenylethane-1,2-diol Other name(s): epoxide hydratase (ambiguous); microsomal epoxide hydratase (ambiguous); epoxide hydrase; microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[a]pyrene-4,5-oxide hydratase; benzo(a)pyrene-4,5-epoxide hydratase; aryl epoxide hydrase (ambiguous); cis-epoxide hydrolase; mEH Systematic name: cis-stilbene-oxide hydrolase Comments: This is a key hepatic enzyme that is involved in the metabolism of numerous xenobiotics, such as 1,3-butadiene oxide, styrene oxide and the polycyclic aromatic hydrocarbon benzo[a]pyrene 4,5- oxide [5—7]. In a series of oxiranes with a lipophilic substituent of sufficient size (styrene oxides), monosubstituted as well as 1,1- and cis-1,2-disubstituted oxiranes serve as substrates or inhibitors of the enzyme. However, trans-1,2-disubstituted, tri-and tetra-substituted oxiranes are not substrates [9]. The reaction involves the formation of an hydroxyalkyl—enzyme intermediate [10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6- oxide hydrolase) [7]. References: 1. Jakoby, W.B. and Fjellstedt, T.A. Epoxidases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 7, Academic Press, New York, 1972, pp. 199–212. 2. Lu, A.Y., Ryan, D., Jerina, D.M., Daly, J.W. and Levin, W. Liver microsomal expoxide hydrase. Solubilization, purification, and characterization. J. Biol. Chem. 250 (1975) 8283–8288. [PMID: 240858] 3. Oesch, F. Purification and specificity of a human microsomal epoxide hydratase. Biochem. J. 139 (1974) 77–88. [PMID: 4463951] 4. Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim. Biophys. Acta 227 (1971) 692–697. [PMID: 4998715] 5. Bellucci, G., Chiappe, C. and Ingrosso, G. Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides. Chirality 6 (1994) 577–582. [PMID: 7986671] 6. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [PMID: 15822179] 7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734] 8. Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [PMID: 4584115] 9. Lacourciere, G.M. and Armstrong, R.N. Microsomal and soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes. Chem. Res. Toxicol. 7 (1994) 121–124. [PMID: 8199297] 10. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] [EC 3.3.2.9 created 2006 (EC 3.3.2.3 part-incorporated 2006)]

EC 3.3.2.10 Common name: soluble epoxide hydrolase

Reaction: an epoxide + H2O = a glycol http://www.enzyme-database.org/newenz.php?sp=off Page 34 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Other name(s): epoxide hydrase (ambiguous); epoxide hydratase (ambiguous); arene-oxide hydratase (ambiguous); aryl epoxide hydrase (ambiguous); trans-stilbene oxide hydrolase; sEH; cytosolic epoxide hydrolase Systematic name: epoxide hydrolase Comments: Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid- phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl—enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6- dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene- A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7]. References: 1. Newman, J.W., Morisseau, C., Harris, T.R. and Hammock, B.D. The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc. Natl. Acad. Sci. USA 100 (2003) 1558–1563. [PMID: 12574510] 2. Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F. and Arand, M. The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase. Proc. Natl. Acad. Sci. USA 100 (2003) 1552–1557. [PMID: 12574508] 3. Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305–340. [PMID: 4584115] 4. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311–333. [PMID: 15822179] 5. Yu, Z., Xu, F., Huse, L.M., Morisseau, C., Draper, A.J., Newman, J.W., Parker, C., Graham, L., Engler, M.M., Hammock, B.D., Zeldin, D.C. and Kroetz, D.L. Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ. Res. 87 (2000) 992–998. [PMID: 11090543] 6. Lacourciere, G.M. and Armstrong, R.N. The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate. J. Am. Chem. Soc. 115 (1993) 10466–10456. 7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734] 8. Zeldin, D.C., Wei, S., Falck, J.R., Hammock, B.D., Snapper, J.R. and Capdevila, J.H. Metabolism of epoxyeicosatrienoic acids by cytosolic epoxide hydrolase: substrate structural determinants of asymmetric catalysis. Arch. Biochem. Biophys. 316 (1995) 443–451. [PMID: 7840649] 9. Haeggström, J., Meijer, J. and Rådmark, O. Leukotriene A4. Enzymatic conversion into 5,6- dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase. J. Biol. Chem. 261 (1986) 6332–6337. [PMID: 3009453] 10. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] [EC 3.3.2.10 created 2006 (EC 3.3.2.3 part-incorporated 2006)]

EC 3.3.2.11 Common name: cholesterol-5,6-oxide hydrolase

Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = cholestane-3β-5α,6β-triol (2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = cholestane-3β-5α,6β-triol For diagram of reactions, click here Glossary: cholesterol = cholest-5-en-3β-ol Other name(s): cholesterol-epoxide hydrolase; ChEH Systematic name: 5,6α-epoxy-5α-cholestan-3β-ol hydrolase Comments: The enzyme appears to work equally well with either epoxide as substrate [3]. The product is a competitive inhibitor of the reaction. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [3].

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References: 1. Levin, W., Michaud, D.P., Thomas, P.E. and Jerina, D.M. Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 α-oxide and certain xenobiotic alkene and arene oxides. Arch. Biochem. Biophys. 220 (1983) 485–494. [PMID: 6401984] 2. Oesch, F., Timms, C.W., Walker, C.H., Guenthner, T.M., Sparrow, A., Watabe, T. and Wolf, C.R. Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5 (1984) 7–9. [PMID: 6690087] 3. Sevanian, A. and McLeod, L.L. Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase. J. Biol. Chem. 261 (1986) 54–59. [PMID: 3941086] 4. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41–59. [PMID: 11154734] 5. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1–51. [PMID: 15748653] [EC 3.3.2.11 created 2006]

EC 3.4.21.87 Transferred entry: now EC 3.4.23.49, omptin. The enzyme is not a , as thought previously, but an aspartate protease. [EC 3.4.21.87 created 1993, deleted 2006]

EC 3.4.23.49 Recommended name: omptin Reaction: Has a virtual requirement for Arg in the P1 position and a slightly less stringent preference for this residue in the P1′ position, which can also contain Lys, Gly or Val. Other name(s): protease VII; protease A; gene ompT proteins; ompT protease; protein a; Pla; protease VII; protease A; OmpT Comments: A product of the ompT gene of Escherichia coli, and associated with the outer membrane. Omptin shows a preference for cleavage between consecutive basic amino acids, but is capable of cleavage when P1′ is a non-basic residue [5,7]. Belongs in peptidase family A26. Links to other databases: CAS registry number: 150770-86-8 References: 1. Grodberg, J., Lundrigan, M.D., Toledo, D.L., Mangel, W.F. and Dunn, J.J. Complete nucleotide sequence and deduced amino acid sequence of the ompT gene of Escherichia coli K-12. Nucleic Acids Res. 16 (1988) 1209 only. [PMID: 3278297] 2. Sugimura, K. and Nishihara, T. Purification, characterization, and primary structure of Escherichia coli protease VII with specificity for paired basic residues: identity of protease VII and ompT. J. Bacteriol. 170 (1988) 5625–5632. [PMID: 3056908] 3. Hanke, C., Hess, J., Schumacher, G. and Goebel, W. Processing by OmpT of fusion proteins carrying the HlyA transport signal during secretion by the Escherichia coli hemolysin transport system. Mol. Gen. Genet. 233 (1992) 42–48. [PMID: 1603076] 4. Dekker, N. Omptin. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds), Handbook of Proteolytic Enzymes, 2nd edn, Elsevier, London, 2004, pp. 212–216. 5. Vandeputte-Rutten, L., Kramer, R.A., Kroon, J., Dekker, N., Egmond, M.R. and Gros, P. Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site. EMBO J. 20 (2001) 5033–5039. [PMID: 11566868] 6. Kramer, R.A., Vandeputte-Rutten, L., de Roon, G.J., Gros, P., Dekker, N. and Egmond, M.R. Identification of essential acidic residues of outer membrane protease OmpT supports a novel active site. FEBS Lett. 505 (2001) 426–430. [PMID: 11576541] 7. McCarter, J.D., Stephens, D., Shoemaker, K., Rosenberg, S., Kirsch, J.F. and Georgiou, G. Substrate specificity of the Escherichia coli outer membrane protease OmpT. J. Bacteriol. 186 (2004) 5919–5925. [PMID: 15317797] [EC 3.4.23.49 created 1993 as EC 3.4.21.87, transferred 2006 to EC 3.4.23.49]

EC 3.5.1.94 Common name: γ-glutamyl-γ-aminobutyrate hydrolase

Reaction: 4-(γ-glutamylamino)butanoate + H2O = 4-aminobutanoate + L-glutamate Other name(s): γ-glutamyl-GABA hydrolase; PuuD; YcjL Systematic name: 4-(γ-glutamylamino)butanoate amidohydrolase Comments: Forms part of a novel putrescine-utilizing pathway in Escherichia coli, in which it has been

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hypothesized that putrescine is first glutamylated to form γ-glutamylputrescine, which is oxidized to 4-(γ-glutamylamino)butanal and then to 4-(γ-glutamylamino)butanoate. The enzyme can also catalyse the reactions of EC 3.5.1.35 (D-) and EC 3.5.1.65 (theanine hydrolase). References: 1. Kurihara, S., Oda, S., Kato, K., Kim, H.G., Koyanagi, T., Kumagai, H. and Suzuki, H. A novel putrescine utilization pathway involves γ-glutamylated intermediates of Escherichia coli K-12. J. Biol. Chem. 280 (2005) 4602–4608. [PMID: 15590624] [EC 3.5.1.94 created 2006]

EC 3.5.1.95 Common name: N-malonylurea hydrolase

Reaction: 3-oxo-3-ureidopropanoate + H2O = malonate + urea For pyrimidine catabolism, click here Other name(s): ureidomalonase Systematic name: 3-oxo-3-ureidopropanoate amidohydrolase (urea- and malonate-forming) Comments: Forms part of the oxidative pyrimidine-degrading pathway in some microorganisms, along with EC 1.17.99.4 (uracil/thymine dehydrogenase) and EC 3.5.2.1 (barbiturase). References: 1. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme, ureidomalonase. Biochem. Biophys. Res. Commun. 286 (2001) 222–226. [PMID: 11485332] 2. Soong, C.L., Ogawa, J., Sakuradani, E. and Shimizu, S. Barbiturase, a novel zinc-containing amidohydrolase involved in oxidative pyrimidine metabolism. J. Biol. Chem. 277 (2002) 7051– 7058. [PMID: 11748240] [EC 3.5.1.95 created 2006]

EC 3.5.1.96 Common name: succinylglutamate desuccinylase

Reaction: N-succinyl-L-glutamate + H2O = succinate + L-glutamate For diagram of arginine catabolism, click here Other name(s): N2-succinylglutamate desuccinylase; SGDS; AstE Systematic name: N-succinyl-L-glutamate amidohydrolase Comments: Requires Co2+ for maximal activity [1]. 2-N-Acetylglutamate is not a substrate. This is the final enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N-succinylarginine dihydrolase), EC 2.6.1.11 (acetylornithine transaminase), EC 1.2.1.71 (succinylglutamate- semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase). References: 1. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882–886. [PMID: 2865249] 2. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314–352. [PMID: 3534538] 3. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Erratum report: Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 51 (1987) 178 only. 4. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280–7290. [PMID: 9393691] 5. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278–4286. [PMID: 9696779] [EC 3.5.1.96 created 2006]

*EC 3.5.2.1 Common name: barbiturase

Reaction: barbiturate + H2O = 3-oxo-3-ureidopropanoate For diagram of pyrimidine catabolism, click here

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Glossary: barbiturate = 6-hydroxyuracil Systematic name: barbiturate amidohydrolase (3-oxo-3-ureidopropanoate-forming) Comments: Contains zinc and is specific for barbiturate as substrate [3]. Forms part of the oxidative pyrimidine- degrading pathway in some microorganisms, along with EC 1.17.99.4 (uracil/thymine dehydrogenase) and EC 3.5.1.95 (N-malonylurea hydrolase). It was previously thought that the end-products of the reaction were malonate and urea but this has since been disproved [2]. May be involved in the regulation of pyrimidine metabolism, along with EC 2.4.2.9, uracil phosphoribosyltransferase. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, CAS registry number: 9025-16-5 References: 1. Hayaishi, O. and Kornberg, A. Metabolism of cytosine, thymine, uracil, and barbituric acid by bacterial enzymes. J. Biol. Chem. 197 (1952) 717–723. [PMID: 12981104] 2. Soong, C.L., Ogawa, J. and Shimizu, S. Novel amidohydrolytic reactions in oxidative pyrimidine metabolism: analysis of the barbiturase reaction and discovery of a novel enzyme, ureidomalonase. Biochem. Biophys. Res. Commun. 286 (2001) 222–226. [PMID: 11485332] 3. Soong, C.L., Ogawa, J., Sakuradani, E. and Shimizu, S. Barbiturase, a novel zinc-containing amidohydrolase involved in oxidative pyrimidine metabolism. J. Biol. Chem. 277 (2002) 7051– 7058. [PMID: 11748240] [EC 3.5.2.1 created 1961, modified 2006]

EC 3.5.3.23 Common name: N-succinylarginine dihydrolase

Reaction: 2-N-succinyl-L-arginine + 2 H2O = 2-N-succinyl-L-ornithine + 2 NH3 + CO2 For diagram of arginine catabolism, click here Other name(s): N2-succinylarginine dihydrolase; arginine succinylhydrolase; SADH; AruB; AstB; N2-succinyl-L- arginine iminohydrolase (decarboxylating) Systematic name: 2-N-succinyl-L-arginine iminohydrolase (decarboxylating) Comments: Arginine, 2-N-acetylarginine and 2-N-glutamylarginine do not act as substrates [3]. This is the second enzyme in the arginine succinyltransferase (AST) pathway for the catabolism of arginine [1]. This pathway converts the carbon skeleton of arginine into glutamate, with the concomitant production of ammonia and conversion of succinyl-CoA into succinate and CoA. The five enzymes involved in this pathway are EC 2.3.1.109 (arginine N-succinyltransferase), EC 3.5.3.23 (N- succinylarginine dihydrolase), EC 2.6.1.81 (succinylornithine transaminase), EC 1.2.1.71 (succinylglutamate semialdehyde dehydrogenase) and EC 3.5.1.96 (succinylglutamate desuccinylase). References: 1. Schneider, B.L., Kiupakis, A.K. and Reitzer, L.J. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J. Bacteriol. 180 (1998) 4278–4286. [PMID: 9696779] 2. Tocilj, A., Schrag, J.D., Li, Y., Schneider, B.L., Reitzer, L., Matte, A. and Cygler, M. Crystal structure of N-succinylarginine dihydrolase AstB, bound to substrate and product, an enzyme from the arginine catabolic pathway of Escherichia coli. J. Biol. Chem. 280 (2005) 15800–15808. [PMID: 15703173] 3. Vander Wauven, C. and Stalon, V. Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia. J. Bacteriol. 164 (1985) 882–886. [PMID: 2865249] 4. Cunin, R., Glansdorff, N., Pierard, A. and Stalon, V. Biosynthesis and metabolism of arginine in bacteria. Microbiol. Rev. 50 (1986) 314–352. [PMID: 3534538] 5. Itoh, Y. Cloning and characterization of the aru genes encoding enzymes of the catabolic arginine succinyltransferase pathway in Pseudomonas aeruginosa. J. Bacteriol. 179 (1997) 7280–7290. [PMID: 9393691] [EC 3.5.3.23 created 2006]

*EC 3.6.3.5 Common name: Zn2+-exporting ATPase 2+ 2+ Reaction: ATP + H2O + Zn in = ADP + phosphate + Zn out Other name(s): Zn(II)-translocating P-type ATPase; P1B-type ATPase; AtHMA4 Systematic name: ATP phosphohydrolase (Zn2+-exporting) Comments: A P-type ATPase that undergoes covalent phosphorylation during the transport cycle. This enzyme also exports Cd2+ and Pb2+. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB http://www.enzyme-database.org/newenz.php?sp=off Page 38 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

References: 1. Beard, S.J., Hashim, R., Membrillo-Hernández, J., Hughes, M.N. and Poole, R.K. Zinc(II) tolerance in Escherichia coli K-12: evidence that the zntA gene (o732) encodes a cation transport ATPase. Mol. Microbiol. 25 (1997) 883–891. [PMID: 9364914] 2. Rensing, C., Mitra, B. and Rosen, B.P. The zntA gene of Escherichia coli encodes a Zn(II)- translocating P-type ATPase. Proc. Natl. Acad. Sci. USA 94 (1997) 14326–14331. [PMID: 9405611] 3. Rensing, C., Sun, Y., Mitra, B. and Rosen, B.P. Pb(II)-translocating P-type . J. Biol. Chem. 273 (1998) 32614–32617. [PMID: 9830000] 4. Mills, R.F., Francini, A., Ferreira da Rocha, P.S., Baccarini, P.J., Aylett, M., Krijger, G.C. and Williams, L.E. The plant P1B-type ATPase AtHMA4 transports Zn and Cd and plays a role in detoxification of transition metals supplied at elevated levels. FEBS Lett. 579 (2005) 783–791. [PMID: 15670847] 5. Eren, E. and Argüello, J.M. Arabidopsis HMA2, a divalent heavy metal-transporting P(IB)-type ATPase, is involved in cytoplasmic Zn2+ homeostasis. Plant Physiol. 136 (2004) 3712–3723. [PMID: 15475410] [EC 3.6.3.5 created 2000, modified 2001, modified 2006]

*EC 3.6.3.44 Common name: xenobiotic-transporting ATPase

Reaction: ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout Other name(s): multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting) Systematic name: ATP phosphohydrolase (xenobiotic-exporting) Comments: ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP- binding domains. Does not undergo phosphorylation during the transport process. The enzyme from Gram-positive bacteria and eukaryotic cells export a number of drugs, with unusual specificity, covering various groups of unrelated substances, while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them transport glutathione—drug conjugates. Some also show some 'flippase' (phospholipid- translocating ATPase; EC 3.6.3.1) activity. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG References: 1. Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmac. Toxicol. 36 (1996) 161–183. [PMID: 8725386] 2. Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude- Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression. Adv. Enzyme Regul. 36 (1996) 351–363. [PMID: 8869755] 3. Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv. Enzyme Regul. 37 (1997) 321–333. [PMID: 9381978] 4. Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the Mr 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58 (1998) 5130–5136. [PMID: 9823323] 5. van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31–36. [PMID: 9693718] 6. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998. 7. Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995) 320–329. [PMID: 7614555] 8. Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M. bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. J. Bacteriol. 177 (1995) 1536–1543. [PMID: 7883711] 9. Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167–25172. [PMID: 8810273] [EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006]

EC 3.6.3.45 Deleted entry: steroid-transporting ATPase. Now included with EC 3.6.3.44, xenobiotic-transporting ATPase [EC 3.6.3.45 created 2000, deleted 2006] http://www.enzyme-database.org/newenz.php?sp=off Page 39 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

*EC 4.1.1.21 Common name: phosphoribosylaminoimidazole carboxylase Reaction: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D- ribosyl)imidazole + CO2 For diagram of the late stages of purine biosynthesis, click here Other name(s): 5-phosphoribosyl-5-aminoimidazole carboxylase; 5-amino-1-ribosylimidazole 5-phosphate carboxylase; AIR carboxylase; 1-(5-phosphoribosyl)-5-amino-4-imidazolecarboxylate carboxy- lyase; ADE2; class II PurE Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate carboxy-lyase Comments: While this is the reaction that occurs in vertebrates during purine biosynthesis, two enzymes are required to carry out the same reaction in Escherichia coli, namely EC 6.3.4.18, 5- (carboxyamino)imidazole ribonucleotide synthase and EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase [3]. 5-Carboxyamino-1-(5-phospho-D-ribosyl)imidazole is not a substrate. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 9032-04-6 References: 1. Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5- amino-1-ribosyl-4-imidazolecarboxylic acid 5′-phosphate from 5-amino-1-ribosylimidazole 5′- phosphate and carbon dioxide. J. Biol. Chem. 234 (1959) 1799–1805. [PMID: 13672967] 2. Firestine, S.M., Poon, S.W., Mueller, E.J., Stubbe, J. and Davisson, V.J. Reactions catalyzed by 5-aminoimidazole ribonucleotide carboxylases from Escherichia coli and Gallus gallus: a case for divergent catalytic mechanisms. Biochemistry 33 (1994) 11927–11934. [PMID: 7918411] 3. Firestine, S.M., Misialek, S., Toffaletti, D.L., Klem, T.J., Perfect, J.R. and Davisson, V.J. Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis. Arch. Biochem. Biophys. 351 (1998) 123–134. [PMID: 9500840] [EC 4.1.1.21 created 1961, modified 2000, modified 2006]

EC 4.1.1.86 Common name: diaminobutyrate decarboxylase

Reaction: L-2,4-diaminobutanoate = propane-1,3-diamine + CO2 For diagram of ectoine biosynthesis, click here Other name(s): DABA DC; L-2,4-diaminobutyrate decarboxylase Systematic name: L-2,4-diaminobutanoate carboxy-lyase Comments: A pyridoxal-phosphate protein that requires a divalent cation for activity [1]. 4-N-Acetyl-L-2,4- diaminobutanoate, 2,3-diaminopropanoate, ornithine and lysine are not substrates. Found in the proteobacteria Haemophilus influenzae and Acinetobacter baumannii. In the latter, it is a product of the ddc gene that also encodes EC 2.6.1.76, diaminobutyrate—2-oxoglutarate transaminase, which can supply the substrate for the decarboxylase. References: 1. Yamamoto, S., Tsuzaki, Y., Tougou, K. and Shinoda, S. Purification and characterization of L- 2,4-diaminobutyrate decarboxylase from Acinetobacter calcoaceticus. J. Gen. Microbiol. 138 (1992) 1461–1465. [PMID: 1512577] 2. Ikai, H. and Yamamoto, S. Cloning and expression in Escherichia coli of the gene encoding a novel L-2,4-diaminobutyrate decarboxylase of Acinetobacter baumannii. FEMS Microbiol. Lett. 124 (1994) 225–228. [PMID: 7813892] 3. Ikai, H. and Yamamoto, S. Identification and analysis of a gene encoding L-2,4- diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production pathway in Acinetobacter baumannii. J. Bacteriol. 179 (1997) 5118–5125. [PMID: 9260954] [EC 4.1.1.86 created 2006]

*EC 4.1.2.8 Common name: indole-3-glycerol-phosphate lyase Reaction: (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate = indole + D-glyceraldehyde 3-phosphate For diagram of reaction, click here Other name(s): α; TSA; indoleglycerolphosphate aldolase; indole glycerol phosphate hydrolase; indole synthase; indole-3-glycerolphosphate D-glyceraldehyde-3-phosphate-lyase; indole-3-glycerol phosphate lyase; IGL; BX1 http://www.enzyme-database.org/newenz.php?sp=off Page 40 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

Systematic name: (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate D-glyceraldehyde-3-phosphate-lyase Comments: Forms part of the defence mechanism against insects and microbial pathogens in the grass family, Gramineae, where it catalyses the first committed step in the formation of the cyclic hydroxamic acids 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-2H-1,4- benzoxazin-3(4H)-one (DIMBOA) [1]. This enzyme resembles the α-subunit of EC 4.2.1.20, tryptophan synthase [3], for which, (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate is also a substrate, but, unlike tryptophan synthase, its activity is independent of the β-subunit and free indole is released [2]. References: 1. Yanofsky, C. The enzymatic conversion of anthranilic acid to indole. J. Biol. Chem. 223 (1956) 171–184. [PMID: 13376586] 2. Frey, M., Chomet, P., Glawischnig, E., Stettner, C., Grün, S., Winklmair, A., Eisenreich, W., Bacher, A., Meeley, R.B., Briggs, S.P., Simcox, K. and Gierl, A. Analysis of a chemical plant defense mechanism in grasses. Science 277 (1997) 696–699. 3. Frey, M., Stettner, C., Paré, P.W., Schmelz, E.A., Tumlinson, J.H. and Gierl, A. An herbivore elicitor activates the gene for indole emission in maize. Proc. Natl. Acad. Sci. USA 97 (2000) 14801–14806. [PMID: 11106389] 4. Melanson, D., Chilton, M.D., Masters-Moore, D. and Chilton, W.S. A deletion in an indole synthase gene is responsible for the DIMBOA-deficient phenotype of bxbx maize. Proc. Natl. Acad. Sci. USA 94 (1997) 13345–13350. [PMID: 9371848] [EC 4.1.2.8 created 1961, deleted 1972, reinstated 2006]

EC 4.1.3.39 Common name: 4-hydroxy-2-oxovalerate aldolase Reaction: 4-hydroxy-2-oxopentanoate = pyruvate + acetaldehyde Glossary: valerate = pentanoate Other name(s): 4-hydroxy-2-ketovalerate aldolase; HOA; DmpG; 4-hydroxy-2-oxovalerate pyruvate-lyase Systematic name: 4-hydroxy-2-oxopentanoate pyruvate-lyase Comments: Requires Mn2+ for maximal activity [1]. The enzyme from Pseudomonas putida is also stimulated by the presence of NADH [1]. In Pseudomonas species, this enzyme forms part of a bifunctional enzyme with EC 1.2.1.10, acetaldehyde dehydrogenase (acetylating). It catalyses the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol [1]. References: 1. Manjasetty, B.A., Powlowski, J. and Vrielink, A. Crystal structure of a bifunctional aldolase- dehydrogenase: sequestering a reactive and volatile intermediate. Proc. Natl. Acad. Sci. USA 100 (2003) 6992–6997. [PMID: 12764229] 2. Powlowski, J., Sahlman, L. and Shingler, V. Purification and properties of the physically associated meta-cleavage pathway enzymes 4-hydroxy-2-ketovalerate aldolase and aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. J. Bacteriol. 175 (1993) 377– 385. [PMID: 8419288] 3. Manjasetty, B.A., Croteau, N., Powlowski, J. and Vrielink, A. Crystallization and preliminary X-ray analysis of dmpFG-encoded 4-hydroxy-2-ketovalerate aldolase—aldehyde dehydrogenase (acylating) from Pseudomonas sp. strain CF600. Acta Crystallogr. D Biol. Crystallogr. 57 (2001) 582–585. [PMID: 11264589] [EC 4.1.3.39 created 2006]

*EC 4.2.1.60 Common name: 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase

Reaction: (1) (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] = trans-dec-2-enoyl-[acyl-carrier-protein] + H2O (2) (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] = cis-dec-3-enoyl-[acyl-carrier-protein] + H2O Other name(s): D-3-hydroxydecanoyl-[acyl-carrier protein] dehydratase; 3-hydroxydecanoyl-acyl carrier protein dehydrase; 3-hydroxydecanoyl-acyl carrier protein dehydratase; β-hydroxydecanoyl thioester dehydrase; β-hydroxydecanoate dehydrase; β-hydroxydecanoyl thiol ester dehydrase; FabA; β- hydroxyacyl-acyl carrier protein dehydratase; HDDase; β-hydroxyacyl-ACP dehydrase Systematic name: (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] hydro-lyase

Comments: Specific for C10 chain length. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, PDB, CAS registry number: 9030-79-9 References: 1. Kass, L.R., Brock, D.J.H. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. I. Purification and properties. J. Biol. Chem. 242 (1967) 4418–4431. [PMID: 4863739] 2. Brock, D.J.H., Kass, L.R. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. II. Mode of

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action. J. Biol. Chem. 242 (1967) 4432–4440. [PMID: 4863740] 3. Sharma, A., Henderson, B.S., Schwab, J.M. and Smith, J.L. Crystallization and preliminary X-ray analysis of β-hydroxydecanoyl thiol ester dehydrase from Escherichia coli. J. Biol. Chem. 265 (1990) 5110–5112. [PMID: 2180957] 4. Magnuson, K., Jackowski, S., Rock, C.O. and Cronan, J.E., Jr. Regulation of fatty acid biosynthesis in Escherichia coli. Microbiol. Rev. 57 (1993) 522–542. [PMID: 8246839] 5. Bloch, K. Enzymatic synthesis of monounsaturated fatty acids. Acc. Chem. Res. 2 (1969) 193– 202. 6. Wang, H. and Cronan, J.E. Functional replacement of the FabA and FabB proteins of Escherichia coli fatty acid synthesis by Enterococcus faecalis FabZ and FabF homologues. J. Biol. Chem. 279 (2004) 34489–34495. [PMID: 15194690] 7. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636. [EC 4.2.1.60 created 1972, modified 2006]

EC 4.2.1.108 Common name: ectoine synthase

Reaction: 4-N-acetyl-L-2,4-diaminobutanoate = L-ectoine + H2O For diagram of ectoine biosynthesis, click here Glossary: ectoine = (4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylate Other name(s): N-acetyldiaminobutyrate dehydratase; N-acetyldiaminobutanoate dehydratase; L-ectoine synthase; EctC; N4-acetyl-L-2,4-diaminobutanoate hydro-lyase Systematic name: 4-N-acetyl-L-2,4-diaminobutanoate hydro-lyase Comments: Ectoine is an osmoprotectant that is found in halophilic eubacteria. This is the third enzyme in the ectoine-biosynthesis pathway, the other enzymes involved being EC 2.6.1.76, diaminobutyrate—2- oxoglutarate transaminase and EC 2.3.1.178, diaminobutyrate acetyltransferase [1,2]. References: 1. Peters, P., Galinski, E.A. and Truper, H.G. The biosynthesis of ectoine. FEMS Microbiol. Lett. 71 (1990) 157–162. 2. Ono, H., Sawada, K., Khunajakr, N., Tao, T., Yamamoto, M., Hiramoto, M., Shinmyo, A., Takano, M. and Murooka, Y. Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. J. Bacteriol. 181 (1999) 91–99. [PMID: 9864317] 3. Kuhlmann, A.U. and Bremer, E. Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl. Environ. Microbiol. 68 (2002) 772–783. [PMID: 11823218] 4. Louis, P. and Galinski, E.A. Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. Microbiology 143 (1997) 1141–1149. [PMID: 9141677] [EC 4.2.1.108 created 2006]

*EC 4.2.3.9 Common name: aristolochene synthase Reaction: (1) 2-trans,6-trans-farnesyl diphosphate = aristolochene + diphosphate (2) 2-trans,6-trans-farnesyl diphosphate = (+)-(10R)-germacrene A + diphosphate For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here Other name(s): sesquiterpene cyclase; trans,trans-farnesyl diphosphate aristolochene-lyase; trans,trans-farnesyl- diphosphate diphosphate-lyase (cyclizing, aristolochene-forming) Systematic name: 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase (cyclizing, aristolochene-forming) Comments: The initial internal cyclization produces the monocyclic intermediate germacrene A; further cyclization and methyl transfer converts the intermediate into aristolochene. While in some species germacrene A remains as an enzyme-bound intermediate, it has been shown to be a minor product of the reaction in Penicillium roqueforti [5] (see also EC 4.2.3.23, germacrene-A synthase). The enzyme from Penicillium roqueforti requires Mg2+ and Mn2+ for activity. Aristolochene is the likely parent compound for a number of sesquiterpenes produced by filamentous fungi. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB References: 1. Cane, D.E., Prabhakaran, P.C., Oliver, J.S. and McIlwaine, D.B. Aristolochene biosynthesis. Stereochemistry of the deprotonation steps in the enzymatic cyclization of farnesyl

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pyrophosphate. J. Am. Chem. Soc. 112 (1990) 3209–3210. 2. Cane, D.E., Prabhakaran, P.C., Salaski, E.J., Harrison, P.M.H., Noguchi, H. and Rawlings, B.J. Aristolochene biosynthesis and enzymatic cyclization of farnesyl pyrophosphate. J. Am. Chem. Soc. 111 (1989) 8914–8916. 3. Hohn, T.M. and Plattner, R.D. Purification and characterization of the sesquiterpene cyclase aristolochene synthase from Penicillium roqueforti. Arch. Biochem. Biophys. 272 (1989) 137– 143. [PMID: 2544140] 4. Proctor, R.H. and Hohn, T.M. Aristolochene synthase. Isolation, characterization, and bacterial expression of a sesquiterpenoid biosynthetic gene (Ari1) from Penicillium roqueforti. J. Biol. Chem. 268 (1993) 4543–4548. [PMID: 8440737] 5. Calvert, M.J., Ashton, P.R. and Allemann, R.K. Germacrene A is a product of the aristolochene synthase-mediated conversion of farnesylpyrophosphate to aristolochene. J. Am. Chem. Soc. 124 (2002) 11636–11641. [PMID: 12296728] [EC 4.2.3.9 created 1992 as EC 2.5.1.40, transferred 1999 to EC 4.1.99.7, transferred 2000 to EC 4.2.3.9, modified 2006]

EC 4.2.3.22 Common name: germacradienol synthase

Reaction: (1) 2-trans,6-trans-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate (2) 2-trans,6-trans-farnesyl diphosphate = (-)-(7S)-germacrene D Other name(s): germacradienol/germacrene-D synthase Systematic name: 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase [(1E,4S,5E,7R)-germacra-1(10),5-dien- 11-ol-forming] Comments: Requires Mg2+ for activity. H-1si of farnesyl diphosphate is lost in the formation of (1E,4S,5E,7R)- germacra-1(10),5-dien-11-ol. Formation of (-)-germacrene D involves a stereospecific 1,3-hydride shift of H-1si of farnesyl diphosphate. Both products are formed from a common intermediate [2]. Other enzymes produce germacrene D as the sole product using a different mechanism. The enzyme mediates a key step in the biosynthesis of geosmin, a widely occurring metabolite of many streptomycetes, bacteria and fungi [2]. References: 1. Cane, D.E. and Watt, R.M. Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis. Proc. Natl. Acad. Sci. USA 100 (2003) 1547–1551. [PMID: 12556563] 2. He, X. and Cane, D.E. Mechanism and stereochemistry of the germacradienol/germacrene D synthase of Streptomyces coelicolor A3(2). J. Am. Chem. Soc. 126 (2004) 2678–2679. [PMID: 14995166] 3. Gust, B., Challis, G.L., Fowler, K., Kieser, T. and Chater, K.F. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc. Natl. Acad. Sci. USA 100 (2003) 1541–1546. [PMID: 12563033] [EC 4.2.3.22 created 2006]

EC 4.2.3.23 Common name: germacrene-A synthase Reaction: 2-trans,6-trans-farnesyl diphosphate = (+)-(10R)-germacrene A + diphosphate For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here Other name(s): germacrene A synthase; (+)-germacrene A synthase; (+)-(10R)-germacrene A synthase; GAS Systematic name: 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase (germacrene-A-forming) Comments: Requires Mg2+ for activity. While germacrene A is an enzyme-bound intermediate in the biosynthesis of a number of phytoalexins, e.g. EC 4.2.3.9 (aristolochene synthase) from some species and EC 4.2.3.21 (), it is the sole sesquiterpenoid product formed in chicory [1]. References: 1. Bouwmeester, H.J., Kodde, J., Verstappen, F.W., Altug, I.G., de Kraker, J.W. and Wallaart, T.E. Isolation and characterization of two germacrene A synthase cDNA clones from chicory. Plant Physiol. 129 (2002) 134–144. [PMID: 12011345] 2. Prosser, I., Phillips, A.L., Gittings, S., Lewis, M.J., Hooper, A.M., Pickett, J.A. and Beale, M.H. (+)-(10R)-Germacrene A synthase from goldenrod, Solidago canadensis; cDNA isolation, bacterial expression and functional analysis. Phytochemistry 60 (2002) 691–702. [PMID: 12127586] 3. de Kraker, J.W., Franssen, M.C., de Groot, A., König, W.A. and Bouwmeester, H.J. (+)- Germacrene A biosynthesis . The committed step in the biosynthesis of bitter sesquiterpene

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lactones in chicory. Plant Physiol. 117 (1998) 1381–1392. [PMID: 9701594] 4. Calvert, M.J., Ashton, P.R. and Allemann, R.K. Germacrene A is a product of the aristolochene synthase-mediated conversion of farnesylpyrophosphate to aristolochene. J. Am. Chem. Soc. 124 (2002) 11636–11641. [PMID: 12296728] 5. Chang, Y.J., Jin, J., Nam, H.Y. and Kim, S.U. Point mutation of (+)-germacrene A synthase from Ixeris dentata. Biotechnol. Lett. 27 (2005) 285–288. [PMID: 15834787] [EC 4.2.3.23 created 2006]

EC 4.2.3.24 Common name: amorpha-4,11-diene synthase Reaction: 2-trans,6-trans-farnesyl diphosphate = amorpha-4,11-diene + diphosphate Other name(s): amorphadiene synthase Systematic name: 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming) Comments: Requires Mg2+ and Mn2+ for activity. This is a key enzyme in the biosynthesis of the antimalarial endoperoxide artemisinin [3]. Catalyses the formation of both olefinic [e.g. amorpha-4,11-diene, amorpha-4,7(11)-diene, γ-humulene and β-sesquiphellandrene] and oxygenated (e.g. amorpha-4- en-7-ol) sesquiterpenes, with amorpha-4,11-diene being the major product. When geranyl diphosphate is used as a substrate, no monoterpenes are produced [2]. References: 1. Wallaart, T.E., Bouwmeester, H.J., Hille, J., Poppinga, L. and Maijers, N.C. Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin. Planta 212 (2001) 460–465. [PMID: 11289612] 2. Mercke, P., Bengtsson, M., Bouwmeester, H.J., Posthumus, M.A. and Brodelius, P.E. Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch. Biochem. Biophys. 381 (2000) 173–180. [PMID: 11032404] 3. Bouwmeester, H.J., Wallaart, T.E., Janssen, M.H., van Loo, B., Jansen, B.J., Posthumus, M.A., Schmidt, C.O., De Kraker, J.W., König, W.A. and Franssen, M.C. Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52 (1999) 843–854. [PMID: 10626375] 4. Chang, Y.J., Song, S.H., Park, S.H. and Kim, S.U. Amorpha-4,11-diene synthase of Artemisia annua: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis. Arch. Biochem. Biophys. 383 (2000) 178–184. [PMID: 11185551] 5. Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D. and Keasling, J.D. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat. Biotechnol. 21 (2003) 796–802. [PMID: 12778056] 6. Picaud, S., Mercke, P., He, X., Sterner, O., Brodelius, M., Cane, D.E. and Brodelius, P.E. Amorpha-4,11-diene synthase: Mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate. Arch. Biochem. Biophys. 448 (2006) 150–155. [PMID: 16143293] [EC 4.2.3.24 created 2006]

EC 4.2.3.25 Common name: S-linalool synthase

Reaction: geranyl diphosphate + H2O = (3S)-linalool + diphosphate Glossary: (3S)-linalool = (3S)-3,7-dimethylocta-1,6-dien-3-ol Other name(s): LIS; Lis; 3S-linalool synthase Systematic name: geranyl-diphosphate diphosphate-lyase [(3S)-linalool-forming] Comments: Requires Mn2+ or Mg2+ for activity. Neither (S)- nor (R)-linalyl diphosphate can act as substrate for the enzyme from the flower Clarkia breweri [1]. Unlike many other monoterpene synthases, only a single product, (3S)-linalool, is formed. References: 1. Pichersky, E., Lewinsohn, E. and Croteau, R. Purification and characterization of S-linalool synthase, an enzyme involved in the production of floral scent in Clarkia breweri. Arch. Biochem. Biophys. 316 (1995) 803–807. [PMID: 7864636] 2. Lücker, J., Bouwmeester, H.J., Schwab, W., Blaas, J., van der Plas, L.H. and Verhoeven, H.A. Expression of Clarkia S-linalool synthase in transgenic petunia plants results in the accumulation of S-linalyl-β-D-glucopyranoside. Plant J. 27 (2001) 315–324. [PMID: 11532177] 3. Dudareva, N., Cseke, L., Blanc, V.M. and Pichersky, E. Evolution of floral scent in Clarkia: novel patterns of S-linalool synthase gene expression in the C. breweri flower. Plant Cell 8 (1996) 1137–1148. [PMID: 8768373] [EC 4.2.3.25 created 2006] http://www.enzyme-database.org/newenz.php?sp=off Page 44 of 48 The Enzyme Database: New Enzymes 06/27/2006 05:11 PM

EC 4.2.3.26 Common name: R-linalool synthase

Reaction: geranyl diphosphate + H2O = (3R)-linalool + diphosphate Glossary: (3R)-linalool = (3R)-3,7-dimethylocta-1,6-dien-3-ol Other name(s): (3R)-linalool synthase; (-)-3R-linalool synthase Systematic name: geranyl-diphosphate diphosphate-lyase [(3R)-linalool-forming] Comments: Geranyl diphosphate cannot be replaced by isopentenyl diphosphate, dimethylallyl diphosphate, farnesyl diphosphate or geranylgeranyl diphosphate as substrate [1]. Requires Mg2+ or Mn2+ for activity. Unlike many other monoterpene synthases, only a single product, (3R)-linalool, is formed. References: 1. Jia, J.W., Crock, J., Lu, S., Croteau, R. and Chen, X.Y. (3R)-Linalool synthase from Artemisia annua L.: cDNA isolation, characterization, and wound induction. Arch. Biochem. Biophys. 372 (1999) 143–149. [PMID: 10562427] 2. Crowell, A.L., Williams, D.C., Davis, E.M., Wildung, M.R. and Croteau, R. Molecular cloning and characterization of a new linalool synthase. Arch. Biochem. Biophys. 405 (2002) 112–121. [PMID: 12176064] [EC 4.2.3.26 created 2006]

EC 4.4.1.24 Common name: sulfolactate sulfo-lyase Reaction: 3-sulfolactate = pyruvate + bisulfite Other name(s): Suy; SuyAB Systematic name: 3-sulfolactate bisulfite-lyase Comments: Requires iron(II). This inducible enzyme from Paracoccus pantotrophus NKNCYSA forms part of the cysteate-degradation pathway. L-Cysteate [(2S)-2-amino-3-sulfopropanoate] serves as a sole source of carbon and energy for the aerobic growth of bacteria, as an electron acceptor for several sulfate-reducing bacteria, as an electron donor for some nitrate-reducing bacteria and as a substrate for a fermentation in a sulfate-reducing bacterium. References: 1. Rein, U., Gueta, R., Denger, K., Ruff, J., Hollemeyer, K. and Cook, A.M. Dissimilation of cysteate via 3-sulfolactate sulfo-lyase and a sulfate exporter in Paracoccus pantotrophus NKNCYSA. Microbiology 151 (2005) 737–747. [PMID: 15758220] [EC 4.4.1.24 created 2006]

EC 4.4.1.25 Common name: L-cysteate sulfo-lyase

Reaction: L-cysteate + H2O = pyruvate + bisulfite + NH3 Glossary: L-cysteate = (2S)-2-amino-3-sulfopropanoate Other name(s): L-cysteate sulfo-lyase (deaminating); CuyA Systematic name: L-cysteate bisulfite-lyase (deaminating) Comments: A pyridoxal-phosphate protein. D-Cysteine can also act as a substrate, but more slowly. It is converted into pyruvate, sulfide and NH3. This inducible enzyme from the marine bacterium Silicibacter pomeroyi DSS-3 forms part of the cysteate-degradation pathway. References: 1. Denger, K., Smits, T.H.M. and Cook, A.M. L-Cysteate sulpho-lyase, a widespread pyridoxal 5′- phosphate-coupled desulphonative enzyme purified from Silicibacter pomeroyi DSS-3(T). Biochem. J. 394 (2006) 657–664. [PMID: 16302849] [EC 4.4.1.25 created 2006]

EC 5.3.3.14 Common name: trans-2-decenoyl-[acyl-carrier protein] isomerase Reaction: trans-dec-2-enoyl-[acyl-carrier-protein] = cis-dec-3-enoyl-[acyl-carrier-protein] Other name(s): β-hydroxydecanoyl thioester dehydrase; trans-2-cis-3-decenoyl-ACP isomerase; trans-2,cis-3- decenoyl-ACP isomerase; trans-2-decenoyl-ACP isomerase; FabM

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Systematic name: decenoyl-[acyl-carrier-protein] Δ2-trans-Δ3-cis-isomerase Comments: While the enzyme from Escherichia coli is highly specific for the 10-carbon enoyl-ACP, the enzyme from Streptococcus pneumoniae can also use the 12-carbon enoyl-ACP as substrate in vitro but not 14- or 16-carbon enoyl-ACPs [3]. ACP can be replaced by either CoA or N-acetylcysteamine thioesters. The cis-3-enoyl product is required to form unsaturated fatty acids, such as palmitoleic acid and cis-vaccenic acid, in dissociated (or type II) fatty-acid biosynthesis. References: 1. Brock, D.J.H., Kass, L.R. and Bloch, K. β-Hydroxydecanoyl thioester dehydrase. II. Mode of action. J. Biol. Chem. 242 (1967) 4432–4440. [PMID: 4863740] 2. Bloch, K. Enzymatic synthesis of monounsaturated fatty acids. Acc. Chem. Res. 2 (1969) 193– 202. 3. Marrakchi, H., Choi, K.H. and Rock, C.O. A new mechanism for anaerobic unsaturated fatty acid formation in Streptococcus pneumoniae. J. Biol. Chem. 277 (2002) 44809–44816. [PMID: 12237320] 4. Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636. [EC 5.3.3.14 created 2006]

EC 5.4.99.18 Common name: 5-(carboxyamino)imidazole ribonucleotide mutase Reaction: 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxylate For diagram of the late stages of purine biosynthesis, click here Other name(s): N5-CAIR mutase; PurE; N5-carboxyaminoimidazole ribonucleotide mutase; class I PurE Systematic name: 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole carboxymutase Comments: In eubacteria, fungi and plants, this enzyme, along with EC 6.3.4.18, 5-(carboxyamino)imidazole ribonucleotide synthase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates [6]. In the absence of EC 6.3.2.6, phosphoribosylaminoimidazolesuccinocarboxamide synthase, the reaction is reversible [3]. The substrate is readily converted into 5-amino-1-(5-phospho-D-ribosyl)imidazole by non-enzymic decarboxylation [3]. References: 1. Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway. Biochemistry 31 (1992) 5022–5032. [PMID: 1534690] 2. Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J. N5-Carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli. Biochemistry 33 (1994) 2269–2278. [PMID: 8117684] 3. Meyer, E., Kappock, T.J., Osuji, C. and Stubbe, J. Evidence for the direct transfer of the carboxylate of N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) to generate 4-carboxy-5- aminoimidazole ribonucleotide catalyzed by Escherichia coli PurE, an N5-CAIR mutase. Biochemistry 38 (1999) 3012–3018. [PMID: 10074353] 4. Mathews, I.I., Kappock, T.J., Stubbe, J. and Ealick, S.E. Crystal structure of Escherichia coli PurE, an unusual mutase in the purine biosynthetic pathway. Structure 7 (1999) 1395–1406. [PMID: 10574791] 5. Firestine, S.M., Poon, S.W., Mueller, E.J., Stubbe, J. and Davisson, V.J. Reactions catalyzed by 5-aminoimidazole ribonucleotide carboxylases from Escherichia coli and Gallus gallus: a case for divergent catalytic mechanisms. Biochemistry 33 (1994) 11927–11934. [PMID: 7918411] 6. Firestine, S.M., Misialek, S., Toffaletti, D.L., Klem, T.J., Perfect, J.R. and Davisson, V.J. Biochemical role of the Cryptococcus neoformans ADE2 protein in fungal de novo purine biosynthesis. Arch. Biochem. Biophys. 351 (1998) 123–134. [PMID: 9500840] [EC 5.4.99.18 created 2006]

*EC 6.3.2.6 Common name: phosphoribosylaminoimidazolesuccinocarboxamide synthase Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate For diagram of the late stages of purine biosynthesis, click here

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Other name(s): phosphoribosylaminoimidazole-succinocarboxamide synthetase; PurC; SAICAR synthetase; 4-(N- succinocarboxamide)-5-aminoimidazole synthetase; 4-[(N-succinylamino)carbonyl]-5- aminoimidazole ribonucleotide synthetase; SAICARs; phosphoribosylaminoimidazolesuccinocarboxamide synthetase; 5-aminoimidazole-4-N- succinocarboxamide ribonucleotide synthetase Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming) Comments: Forms part of the purine biosynthesis pathway. Links to other databases: BRENDA, ERGO, EXPASY, GO, IUBMB, KEGG, PDB, CAS registry number: 9023-67-0 References: 1. Lukens, L.N. and Buchanan, J.M. Biosynthesis of purines. XXIV. The enzymatic synthesis of 5- amino-1-ribosyl-4-imidazolecarboxylic acid 5′-phosphate from 5-amino-1-ribosylimidazole 5′- phosphate and carbon dioxide. J. Biol. Chem. 234 (1959) 1799–1805. [PMID: 13672967] 2. Parker, J. Identification of the purC gene product of Escherichia coli. J. Bacteriol. 157 (1984) 712–717. [PMID: 6365889] 3. Ebbole, D.J. and Zalkin, H. Cloning and characterization of a 12-gene cluster from Bacillus subtilis encoding nine enzymes for de novo purine nucleotide synthesis. J. Biol. Chem. 262 (1987) 8274–8287. [PMID: 3036807] 4. Chen, Z.D., Dixon, J.E. and Zalkin, H. Cloning of a chicken liver cDNA encoding 5- aminoimidazole ribonucleotide carboxylase and 5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase by functional complementation of Escherichia coli pur mutants. Proc. Natl. Acad. Sci. USA 87 (1990) 3097–3101. [PMID: 1691501] 5. O'Donnell, A.F., Tiong, S., Nash, D. and Clark, D.V. The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway. Genetics 154 (2000) 1239–1253. [PMID: 10757766] 6. Nelson, S.W., Binkowski, D.J., Honzatko, R.B. and Fromm, H.J. Mechanism of action of Escherichia coli phosphoribosylaminoimidazolesuccinocarboxamide synthetase. Biochemistry 44 (2005) 766–774. [PMID: 15641804] [EC 6.3.2.6 created 1961, modified 2000, modified 2006]

*EC 6.3.2.27 Common name: aerobactin synthase

Reaction: 4 ATP + citrate + 2 6-N-acetyl-6-N-hydroxy-L-lysine + 2 H2O = 4 ADP + 4 phosphate + aerobactin For diagram of aerobactin biosynthesis, click here Other name(s): citrate:N6-acetyl-N6-hydroxy-L-lysine ligase (ADP-forming) Systematic name: citrate:6-N-acetyl-6-N-hydroxy-L-lysine ligase (ADP-forming) Comments: Requires Mg2+. Aerobactin is one of a group of high-affinity iron chelators known as siderophores and is produced under conditions of iron deprivation [5]. It is a dihydroxamate comprising two molecules of 6-N-acetyl-6-N-hydroxylysine and one molecule of citric acid. This is the last of the three enzymes involved in its synthesis, the others being EC 1.14.13.59, L-lysine 6- monooxygenase (NADPH) and EC 2.3.1.102, N6-hydroxylysine O-acetyltransferase [3]. Links to other databases: BRENDA, ERGO, EXPASY, IUBMB, KEGG, CAS registry number: 94047-30-0 References: 1. Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell- free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443. 2. Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [PMID: 4313071] 3. Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N6-acetyl-N6-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101. 4. de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [PMID: 2935523] 5. Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [PMID: 15719346] [EC 6.3.2.27 created 2002, modified 2006]

EC 6.3.4.18 Common name: 5-(carboxyamino)imidazole ribonucleotide synthase - Reaction: ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole + HCO3 = ADP + phosphate + 5-carboxyamino- 1-(5-phospho-D-ribosyl)imidazole

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For diagram of the late stages of purine biosynthesis, click here Other name(s): N5-CAIR synthetase; N5-carboxyaminoimidazole ribonucleotide synthetase; PurK Systematic name: 5-amino-1-(5-phospho-D-ribosyl)imidazole:carbon-dioxide ligase (ADP-forming) Comments: In Escherichia coli, this enzyme, along with EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp [3]. Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late stages of purine biosynthesis. References: 1. Meyer, E., Leonard, N.J., Bhat, B., Stubbe, J. and Smith, J.M. Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway. Biochemistry 31 (1992) 5022–5032. [PMID: 1534690] 2. Mueller, E.J., Meyer, E., Rudolph, J., Davisson, V.J. and Stubbe, J. N5-Carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli. Biochemistry 33 (1994) 2269–2278. [PMID: 8117684] 3. Thoden, J.B., Kappock, T.J., Stubbe, J. and Holden, H.M. Three-dimensional structure of N5- carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily. Biochemistry 38 (1999) 15480–15492. [PMID: 10569930] [EC 6.3.4.18 created 2006]

© 2001–2005 IUBMB, Andrew McDonald

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