DOCSLIB.ORG

The Study of Pseudomonas Racemases for the Drug Design and Bioremediation Purposes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Study of Pseudomonas Racemases for the Drug Design and Bioremediation Purposes Fourteenth International Symposium on Recent Advances in Environmental Health Research POSTER SESSION B [FACULTY/SCIENTISTS] 9 | PB THE STUDY OF PSEUDOMONAS RACEMASES FOR THE DRUG DESIGN AND BIOREMEDIATION PURPOSES Hung-Chung Huang1,2, Ansley Scott2 and Paul B. Tchounwou1,2 1NIH/NIMHD RCMI Center for Environmental Heath, College of Science, Engineering, and Technology (CSET), Jackson State University, Jackson, MS 39217, USA 2Department of Biology, CSET, Jackson State University, Jackson, MS 39217, USA Abstract: The Pseudomonas bacteria species have been the focus of research for decades. For example, Pseudomonas aeruginosa is an opportunistic pathogen and associated with serious cross-infections in the hospitals and clinics; and several Pseudomonas sp. (e.g., a safe species, P. putida) have the ability to be used in bioremediation to biodegrade oil. The D-alanine produced by alanine racemase (AlaR) is used for peptidoglycan biosynthesis in bacteria, so AlaR is a good drug design target on P. aeruginosa. Mandelate racemase (MdlR) in P. putida is related to mandelate pathway that has something to do with the ability to degrade organic solvents such as toluene. In addition, both AlaR and MdlR utilize a similar catalytic mechanism. Therefore, the structural and comparative study of AlaR in P. aeruginosa and MdlR in P. putida would help us understand better the catalytic mechanism of both racemases which can contribute to the antibiotic drug design targeting P. aeruginosa and the application of bioremediation (via biodegradation) by Pseudomonas species like P. putida. Due to limited X-ray crystallography structure for the AlaR from P. aeruginosa (one available), ten AlaR high-resolution structures from Geobacillus stearothermophilus would be studied and compared to the one from P. aeruginosa for drug design purpose. Ten MdlR X-ray structures for P. putida were available from RCSB PDB databank and these ten structures would be studied and compared to those 11 AlaR structures mentioned above, in order to understand MdlR’s catalytic mechanism better for bioremediation purposes. We have used VMD program from UIUC to study the crystal water sites around the AlaR active sites via TCL scripting language, and used clustering program plus PERL & R to analyze and identify those conserved water sites important for enzymatic function. These conserved and stable water sites can be useful for drug design purposes targeting AlaR. The similar studies and analyses would be performed on those MdlR structures (to be compared to AlaR) to identify the conserved crystal water sites (around the active site) which are related to and may play a big role in the enzyme’s catalytic function. Due to the similarity of the catalytic mechanism in both AlaR and MdlR, the structural and comparative studies of these two racemases in bacteria can help us to be able to design a specific and potent drug targeting AlaR in P. aeruginosa and perform a capable bioremediation on spilled oil by bacteria like P. putida with a fine-tuned catalytic function of bioengineered and modified MdlR. Keywords: Pseudomonas aeruginosa, Alanine Racemase (AlaR), Pseudomonas putida, Mandelate Racemase (MdlR), cluster analysis, drug design, bioremediation. Acknowledgements: This research supported by the National Institutes of Health/National Institute on Minority Health and Health Disparities Grant #G12MD007581, through the RCMI Center for Environmental Health at Jackson State University. 9 .
Load more

Recommended publications
  • Dr. Martin St. Maurice's Publications
    Dr. Martin St. Maurice’s Publications 2013 Lin, Y., and St. Maurice, M. 2013. The structure of allophanate hydrolase from Granulibacter bethesdensis provides insights into substrate specificity in the amidase signature family. Biochemistry. 52: 690-700. 2012 Waldrop, G.L., Holden, H.M., and St. Maurice, M. 2012. The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms. Protein Science 21(11):1597-1619. Adina-Zada, A., Sereeruk, C., Jitrapakdee, S., Zeczycki, T.N., St. Maurice, M., Cleland, W.W., Wallace, J.C., and Attwood, P.V. 2012. Roles of Arg427 and Arg472 in the binding and allosteric effects of acetyl CoA in pyruvate carboxylase. Biochemistry 51(41): 1597-1619. 2011 Adina-Zada, A., Hazra, R., Sereeruk, C., Jitrapakdee, S., Zeczycki, T.N., St. Maurice, M., Cleland, W.W., Wallace, J.C., and Attwood, P.V. 2011. Probing the allosteric activation of pyruvate carboxylase using 2′,3′-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate as a fluorescent mimic of the allosteric activator acetyl CoA. Arch. Biochem. Biophys. 117-126. Zeczycki, T.N., Menefee, A.L., Jitrapakdee, S., Wallace, J.C., Attwood, P.V., St. Maurice, M. and Cleland, W.W. 2011. Activation and inhibition of pyruvate carboxylase from Rhizobium etli. Biochemistry. 9694-9707. Lietzan, A.D., Menefee, A.L., Zeczycki, T.N., Kumar, S., Attwood, P.V., Wallace, J.C., Cleland, W.W. and St. Maurice, M. 2011. Interaction between the biotin carrier domain and the biotin carboxylase domain in the structure of Rhizobium etli pyruvate carboxylase. Biochemistry. 9708-9723. Zeczycki, T.N., Menefee, A.L., Adina-Zada, A., Surinya, K.H., Wallace, J.C., Attwood, P.V., St.
    [Show full text]
  • Letters to Nature
    letters to nature Received 7 July; accepted 21 September 1998. 26. Tronrud, D. E. Conjugate-direction minimization: an improved method for the re®nement of macromolecules. Acta Crystallogr. A 48, 912±916 (1992). 1. Dalbey, R. E., Lively, M. O., Bron, S. & van Dijl, J. M. The chemistry and enzymology of the type 1 27. Wolfe, P. B., Wickner, W. & Goodman, J. M. Sequence of the leader peptidase gene of Escherichia coli signal peptidases. Protein Sci. 6, 1129±1138 (1997). and the orientation of leader peptidase in the bacterial envelope. J. Biol. Chem. 258, 12073±12080 2. Kuo, D. W. et al. Escherichia coli leader peptidase: production of an active form lacking a requirement (1983). for detergent and development of peptide substrates. Arch. Biochem. Biophys. 303, 274±280 (1993). 28. Kraulis, P.G. Molscript: a program to produce both detailed and schematic plots of protein structures. 3. Tschantz, W. R. et al. Characterization of a soluble, catalytically active form of Escherichia coli leader J. Appl. Crystallogr. 24, 946±950 (1991). peptidase: requirement of detergent or phospholipid for optimal activity. Biochemistry 34, 3935±3941 29. Nicholls, A., Sharp, K. A. & Honig, B. Protein folding and association: insights from the interfacial and (1995). the thermodynamic properties of hydrocarbons. Proteins Struct. Funct. Genet. 11, 281±296 (1991). 4. Allsop, A. E. et al.inAnti-Infectives, Recent Advances in Chemistry and Structure-Activity Relationships 30. Meritt, E. A. & Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505± (eds Bently, P. H. & O'Hanlon, P. J.) 61±72 (R. Soc. Chem., Cambridge, 1997).
    [Show full text]
  • Exploring the Chemistry and Evolution of the Isomerases
    Exploring the chemistry and evolution of the isomerases Sergio Martínez Cuestaa, Syed Asad Rahmana, and Janet M. Thorntona,1 aEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom Edited by Gregory A. Petsko, Weill Cornell Medical College, New York, NY, and approved January 12, 2016 (received for review May 14, 2015) Isomerization reactions are fundamental in biology, and isomers identifier serves as a bridge between biochemical data and ge- usually differ in their biological role and pharmacological effects. nomic sequences allowing the assignment of enzymatic activity to In this study, we have cataloged the isomerization reactions known genes and proteins in the functional annotation of genomes. to occur in biology using a combination of manual and computa- Isomerases represent one of the six EC classes and are subdivided tional approaches. This method provides a robust basis for compar- into six subclasses, 17 sub-subclasses, and 245 EC numbers cor- A ison and clustering of the reactions into classes. Comparing our responding to around 300 biochemical reactions (Fig. 1 ). results with the Enzyme Commission (EC) classification, the standard Although the catalytic mechanisms of isomerases have already approach to represent enzyme function on the basis of the overall been partially investigated (3, 12, 13), with the flood of new data, an integrated overview of the chemistry of isomerization in bi- chemistry of the catalyzed reaction, expands our understanding of ology is timely. This study combines manual examination of the the biochemistry of isomerization. The grouping of reactions in- chemistry and structures of isomerases with recent developments volving stereoisomerism is straightforward with two distinct types cis-trans in the automatic search and comparison of reactions.
    [Show full text]
  • SI Appendix Index 1
    SI Appendix Index Calculating chemical attributes using EC-BLAST ................................................................................ 2 Chemical attributes in isomerase reactions ............................................................................................ 3 Bond changes …..................................................................................................................................... 3 Reaction centres …................................................................................................................................. 5 Substrates and products …..................................................................................................................... 6 Comparative analysis …........................................................................................................................ 7 Racemases and epimerases (EC 5.1) ….................................................................................................. 7 Intramolecular oxidoreductases (EC 5.3) …........................................................................................... 8 Intramolecular transferases (EC 5.4) ….................................................................................................. 9 Supporting references …....................................................................................................................... 10 Fig. S1. Overview …............................................................................................................................
    [Show full text]
  • Supporting Information for Proteomics DOI 10.1002/Pmic.200600987
    Supporting Information for Proteomics DOI 10.1002/pmic.200600987 Lars Whlbrand, Birte Kallerhoff, Daniela Lange, Peter Hufnagel, Jrgen Thiermann, Richard Reinhardt and Ralf Rabus Functional proteomic view of metabolic regulation in “Aromatoleum aromaticum” strain EbN1 ª 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.proteomics-journal.com Content 1. General proteome features Page Experimental outline of the presented study with “Aromatoleum aromaticum” 1-2 strain EbN1 (Fig. 1.1.) Spot pattern comparison of differently visualized 2DE gels (Fig. 1.2.) 1-3 Principle component analysis of the proteins for each analyzed 2D DIGE gel 1-4 of all main physiological groups (Fig. 1.3.) Fold changes in protein abundance of all identified proteins (Fig 1-5 Number of regulated as well as not regulated protein spots on the 2DE gels 1-6 and their share of total protein (Table 1.1.) Mean average ratio of not regulated protein spots of the three main 1-7 physiological groups (Table 1.2.) Mean average ratios of not regulated proteins, identified in all three main 1-8 physiological groups (Table 1.3.) Proteins identified in this study (Table 1.4.) 1-9 2. Cellular functions* 2.1. DNA replication, recombination and repair 2-2 2.1.1. DNA replication 2-2 2.2. Transcription 2-4 2.2.1. DNA-dependent RNA polymerase and sigma factors 2-5 2.2.2. Factors affecting RNA polymerase 2-5 2.2.3. Classes of transcriptional regulators 2-5 2.3. Translation 2-6 2.3.1. tRNA synthesis 2-6 2.3.2. tRNA/rRNA modification 2-7 2.3.3.
    [Show full text]
  • Oup Proeng Gzy011 135..145 ++
    Protein Engineering, Design & Selection, 2018, vol. 31 no. 4, pp. 135–145 doi: 10.1093/protein/gzy011 Advance Access Publication Date: 30 May 2018 Original Article Original Article A platform for chemical modification of mandelate racemase: characterization of the C92S/C264S and γ-thialysine 166 variants Downloaded from https://academic.oup.com/peds/article/31/4/135/5025590 by guest on 30 September 2021 Mitesh Nagar1, Himank Kumar1, and Stephen L. Bearne1,2,* 1Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4R2, and 2Department of Chemistry, Dalhousie University, Halifax, NS, Canada B3H 4R2 *To whom correspondence should be addressed. E-mail: [email protected] Edited by Miroslaw Cygler Received 7 February 2018; Revised 28 April 2018; Editorial Decision 30 April 2018; Accepted 3 May 2018 Abstract Mandelate racemase (MR) serves as a paradigm for our understanding of enzyme-catalyzed deprotona- tion of a carbon acid substrate. To facilitate structure–function studies on MR using non-natural amino acid substitutions, we engineered the Cys92Ser/Cys264Ser variant (dmMR) as a platform for introdu- cingCysresiduesatspecific locations for subsequent covalent modification. While the highly reactive thiol of Cys furnishes a site for chemical modification, site-specificity requires that other Cys residues be non-reactive or replaced by a non-reactive amino acid, especially if chemical modification is con- ducted under denaturing conditions. The catalytic efficiency of dmMR is reduced only ~2-fold relative to wild-type MR, making dmMR a viable platform for the site-specificintroductionofCys.Asan example, the inactive Lys166Cys variant of dmMR was treated with ethylenimine under denaturing con- ditions to replace the Brønsted acid-base catalyst Lys 166 with the non-natural amino acid γ-thialysine.
    [Show full text]
  • Impact of Temperature on the Time Required for the Establishment of Primordial Biochemistry, and for the Evolution of Enzymes
    Impact of temperature on the time required for the establishment of primordial biochemistry, and for the evolution of enzymes Randy B. Stockbridge, Charles A. Lewis, Jr., Yang Yuan, and Richard Wolfenden1 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 Contributed by Richard Wolfenden, September 29, 2010 (sent for review August 1, 2010) All reactions are accelerated by an increase in temperature, but the magnitude of that effect on very slow reactions does not seem to have been fully appreciated. The hydrolysis of polysaccharides, for example, is accelerated 190,000-fold when the temperature is raised from 25 to 100 °C, while the rate of hydrolysis of phosphate monoester dianions increases 10,300,000-fold. Moreover, the slow- est reactions tend to be the most heat-sensitive. These tendencies collapse, by as many as five orders of magnitude, the time that would have been required for early chemical evolution in a warm environment. We propose, further, that if the catalytic effect of a “proto-enzyme”—like that of modern enzymes—were mainly enthalpic, then the resulting rate enhancement would have in- creased automatically as the environment became cooler. Several powerful nonenzymatic catalysts of very slow biological reactions, notably pyridoxal phosphate and the ceric ion, are shown to meet that criterion. Taken together, these findings greatly reduce the time that would have been required for early chemical evolution, countering the view that not enough time has passed for life to Fig. 1. Half-lives (t1∕2) and first order rate constants (k) of some biological have evolved to its present level of complexity.
    [Show full text]
  • Biochemical Characterization of Alanine Racemase- a Spore Protein Produced by Bacillus Anthracis
    BMB reports Biochemical characterization of Alanine racemase- a spore protein produced by Bacillus anthracis Shivani Kanodia1,*, Shivangi Agarwal1,*, Priyanka Singh1,*, Shivani Agarwal2, Preeti Singh1 & Rakesh Bhatnagar1,* 1Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi-110067, India, 2Gene Regulation Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi-110067, India Alanine racemase catalyzes the interconversion of L-alanine and racemization proceeds through a two-base mechanism that in- D-alanine and plays a crucial role in spore germination and cell volves lysine (pyridoxal 5'-phosphate binding residue) and ty- wall biosynthesis. In this study, alanine racemase produced by rosine (plays a role in binding/catalysis). Crystallographic analysis Bacillus anthracis was expressed and purified as a monomer in of B. stearothermophilus alanine racemase has shown that the resi- Escherichia coli and the importance of lysine 41 in the cofactor dues at the active site play a role in its racemization (5). Based on binding octapeptide and tyrosine 270 in catalysis was evaluated. its known structure, it is plausible that B. anthracis produces ala- The native enzyme exhibited an apparent Km of 3 mM for L-ala- nine racemase via an analogous catalytic site, wherein Lys41 and nine, and a Vmax of 295 μmoles/min/mg, with the optimum activ- Tyr270 remove α-hydrogen from the alanyl-PLP aldimine and pro- ity occurring at 37oC and a pH of 8-9. The activity observed in the tonate the carbanion to induce racemization. absence of exogenous pyridoxal 5 -phosphaté suggested that the Immunoproteome analysis of the spore antigens produced cofactor is bound to the enzyme.
    [Show full text]
  • Cloning, Biochemical Characterization and Inhibition of Alanine Racemase from Streptococcus Iniae
    bioRxiv preprint doi: https://doi.org/10.1101/611251; this version posted April 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Cloning, Biochemical Characterization and Inhibition of Alanine racemase from Streptococcus iniae Murtala Muhammad, Yangyang Li, Siyu Gong, Yanmin Shi, Jiansong Ju, Baohua Zhao*, Dong Liu* College of Life Science, Hebei Normal University, Shijiazhuang 050024, China; *Correspondence: Baohua Zhao and Dong Liu; E-mail: [email protected], [email protected]; College of Life Science, Hebei Normal University, Shijiazhuang 050024, China. Running Title: Inhibitors of alanine racemase Summary statement: Antimicrobial target 1 bioRxiv preprint doi: https://doi.org/10.1101/611251; this version posted April 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Streptococcus iniae is a pathogenic and zoonotic bacteria that impacted high mortality to many fish species, as well as capable of causing serious disease to humans. Alanine racemase (Alr, EC 5.1.1.1) is a pyridoxal-5′-phosphate (PLP)-containing homodimeric enzyme that catalyzes the racemization of L-alanine and D-alanine. In this study, we purified alanine racemase from the pathogenic strain of S. iniae, determined its biochemical characteristics and inhibitors. The alr gene has an open reading frame (ORF) of 1107 bp, encoding a protein of 369 amino acids, which has a molecular mass of 40 kDa. The optimal enzyme activity occurred at 35°C and a pH of 9.5.
    [Show full text]
  • Phyre 2 Results for P29208
    Email [email protected] Description P29208 Thu Jan 5 11:45:36 GMT Date 2012 Unique Job 0bd634b8f8620003 ID Detailed template information # Template Alignment Coverage 3D Model Confidence % i.d. Template Information PDB header:lyase Chain: A: PDB Molecule:o-succinylbenzoate synthase; 1 c3gc2A_ Alignment 100.0 86 PDBTitle: 1.85 angstrom crystal structure of o-succinylbenzoate synthase from2 salmonella typhimurium in complex with succinic acid PDB header:lyase Chain: A: PDB Molecule:tlr1174 protein; 2 c2oztA_ 100.0 20 Alignment PDBTitle: crystal structure of o-succinylbenzoate synthase from2 thermosynechococcus elongatus bp-1 PDB header:metal binding protein Chain: A: PDB Molecule:enzyme of enolase superfamily; 3 c3px5A_ 100.0 19 Alignment PDBTitle: structure of efi enolase target en500555, a putative dipeptide2 epimerase: apo structure PDB header:isomerase 4 c1jpmB_ Alignment 100.0 20 Chain: B: PDB Molecule:l-ala-d/l-glu epimerase; PDBTitle: l-ala-d/l-glu epimerase PDB header:lyase Chain: A: PDB Molecule:menc; 5 c2pgeA_ 100.0 23 Alignment PDBTitle: crystal structure of menc from desulfotalea psychrophila2 lsv54 PDB header:isomerase Chain: E: PDB Molecule:mandelate racemase/muconate 6 c3q45E_ Alignment 100.0 19 lactonizing enzyme family; PDBTitle: crystal structure of dipeptide epimerase from cytophaga hutchinsonii2 complexed with mg and dipeptide d-ala-l-val PDB header:isomerase Chain: A: PDB Molecule:chloromuconate cycloisomerase; 7 c1nu5A_ 100.0 16 Alignment PDBTitle: crystal structure of pseudomonas sp. p51 chloromuconate lactonizing2
    [Show full text]
  • The Enolase Superfamily: a General Strategy for Enzyme-Catalyzed Abstraction of the R-Protons of Carboxylic Acids†
    + + Biochemistry 1996, 35, 16489-16501 16489 The Enolase Superfamily: A General Strategy for Enzyme-Catalyzed Abstraction of the R-Protons of Carboxylic Acids† ,‡ §,| ⊥,# Patricia C. Babbitt,* Miriam S. Hasson, Joseph E. Wedekind, David R. J. Palmer,r William C. Barrett,r ⊥ ⊥ § ‡ , George H. Reed, Ivan Rayment, Dagmar Ringe, George L. Kenyon, and John A. Gerlt* r Department of Pharmaceutical Chemistry, UniVersity of California, San Francisco, California 94143-0446, Departments of Biochemistry and Chemistry and Rosenstiel Center for Basic Biomedical Research, Brandeis UniVersity, Waltham, Massachusetts 02154-9110, The Institute for Enzyme Research and Department of Biochemistry, UniVersity of Wisconsin, Madison, Wisconsin 53706, and Department of Biochemistry, UniVersity of Illinois, Urbana, Illinois 61801 ReceiVed July 5, 1996X ABSTRACT: We have discovered a superfamily of enzymes related by their ability to catalyze the abstraction of the R-proton of a carboxylic acid to form an enolic intermediate. Although each reaction catalyzed by these enzymes is initiated by this common step, their overall reactions (including racemization, â-elimination of water, â-elimination of ammonia, and cycloisomerization) as well as the stereochemical consequences (syn Vs anti) of the â-elimination reactions are diverse. Analysis of sequence and structural similarities among these proteins suggests that all of their chemical reactions are mediated by a common active site architecture modified through evolution to allow the enolic intermediates to partition to different products in their respective active sites Via different overall mechanisms. All of these enzymes retain the ability to catalyze the thermodynamically difficult step of proton abstraction. These homologous proteins, designated the “enolase superfamily”, include enolase as well as more metabolically specialized enzymes: mandelate racemase, galactonate dehydratase, glucarate dehydratase, muconate-lactonizing enzymes, N-acylamino acid racemase, â-methylaspartate ammonia-lyase, and o-succinylbenzoate synthase.
    [Show full text]
  • Α-Methylacyl-Coa Racemase and Argininosuccinate Lyase
    A460etukansi.fm Page 1 Friday, May 26, 2006 11:40 AM A 460 OULU 2006 A 460 UNIVERSITY OF OULU P.O. Box 7500 FI-90014 UNIVERSITY OF OULU FINLAND ACTA UNIVERSITATIS OULUENSIS ACTA UNIVERSITATIS OULUENSIS ACTA A SERIES EDITORS SCIENTIAE RERUM Prasenjit Bhaumik NATURALIUM Prasenjit Bhaumik Prasenjit ASCIENTIAE RERUM NATURALIUM Professor Mikko Siponen PROTEIN CRYSTALLOGRAPHIC BHUMANIORA STUDIES TO UNDERSTAND Professor Harri Mantila THE REACTION MECHANISM CTECHNICA Professor Juha Kostamovaara OF ENZYMES: DMEDICA α Professor Olli Vuolteenaho -METHYLACYL-CoA RACEMASE AND ESCIENTIAE RERUM SOCIALIUM Senior assistant Timo Latomaa ARGININOSUCCINATE LYASE FSCRIPTA ACADEMICA Communications Officer Elna Stjerna GOECONOMICA Senior Lecturer Seppo Eriksson EDITOR IN CHIEF Professor Olli Vuolteenaho EDITORIAL SECRETARY Publication Editor Kirsti Nurkkala FACULTY OF SCIENCE, DEPARTMENT OF BIOCHEMISTRY, BIOCENTER OULU, ISBN 951-42-8090-3 (Paperback) UNIVERSITY OF OULU ISBN 951-42-8091-1 (PDF) ISSN 0355-3191 (Print) ISSN 1796-220X (Online) ACTA UNIVERSITATIS OULUENSIS A Scientiae Rerum Naturalium 460 PRASENJIT BHAUMIK PROTEIN CRYSTALLOGRAPHIC STUDIES TO UNDERSTAND THE REACTION MECHANISM OF ENZYMES: α-METHYLACYL-COA RACEMASE AND ARGININOSUCCINATE LYASE Academic Dissertation to be presented with the assent of the Faculty of Science, University of Oulu, for public discussion in Kuusamonsali (Auditorium YB210), Linnanmaa, on June 6th, 2006, at 12 noon OULUN YLIOPISTO, OULU 2006 Copyright © 2006 Acta Univ. Oul. A 460, 2006 Supervised by Professor Rik Wierenga Reviewed
    [Show full text]