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Mycobacterium Tuberculosis Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 162 Structural Studies of a Xyloglucan Endotransglycosylase from Populus tremula x tremuloides and Three Conserved Hypothetical Proteins from Mycobacterium tuberculosis PATRIK JOHANSSON ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6214 UPPSALA ISBN 91-554-6513-7 2006 urn:nbn:se:uu:diva-6738 ! " # $%%& !'%% ( ) ( ( *) )+ ,) - . )+ / ) *+ $%%&+ 0 0 ( 1 . ( ,) ) * ( + 2 + &$+ &3 + + 405 36##6&#!67+ ,) ) ) ( ( (( ( - + 1 1., - 6 8+ ,) ( ( 1., 9 ) +: ;+ ,) ) ) - 1., ) ) - ) ) 1.,6 ) + < = ) ( ) ) + ) > ( ) 6 ) ( ( ( ( ) ! 8 - + ? ) ) ( ) ) $7% %$& %!%+ $7% ( @A ( - ) 8 6$6 ) ( " + - ) 6 ( ) " 9 $7% ( ( ) ) ( ) 9+ ,) ( ! %$& ) 6 ) ( + %$& ) - ( 9 ) "6 ) B6) ) + - ( ) ) C ) %$&+ %!% ) ) "6) ( ) ( - ) ( + ,) ( ) 8 8 ) %!% )+ 2 ( C ) ( ( ! ( 6 ) %!% - ( ) ) ( ) + # $ % ) ( ( ) & ' ( )( ) *+,( ( -./*012 ( $ D * 8 / ) $%%& 4005 &#6&$ 405 36##6&#!67 ' ''' 6&7!: <) 'CC +8+C E F ' ''' 6&7!:= A world of dew and within every dewdrop a world of struggle Kobayashi Issa (1762-1826) List of publications This thesis consists of a comprehensive summary based on the following papers. In the text, the papers will be referred to by their roman numerals. I Johansson P., Brumer H., Baumann M.J., Kallas Å.M., Henriks- son H., Denman S.E., Teeri T.T., Jones T.A. (2003). Crystalliza- tion and preliminary X-ray analysis of a xyloglucan endotrans- glycosylase from Populus tremula x tremuloides. Acta Cryst. D59, 535-537. II Johansson P., Brumer H., Baumann M.J., Kallas Å.M., Henriks- son H., Denman S.E., Teeri T.T., Jones T.A. (2004). Crystal structures of a poplar xyloglucan endotransglycosylase reveal de- tails of transglycosylation acceptor binding. Plant Cell 16 (4), 874-886. III Johansson P., Unge T., Cronin A., Arand M., Bergfors T., Jones T.A., Mowbray S.L. (2005). Structure of an atypical epoxide hy- drolase from Mycobacterium tuberculosis gives insights into its function. JMB 351 (5), 1048-1056. IV Castell A., Johansson P., Unge T., Jones T.A., Bäckbo K. (2005). Rv0216, a conserved hypothetical protein from Mycobacterium tuberculosis that is essential for bacterial survival during infec- tion, has a double hotdog fold. Protein science 14 (7), 1850- 1862. V Johansson P., Castell A., Jones T.A., Bäckbro K. (2006). Struc- ture and function of Rv0130, a conserved hypothetical protein from Mycobacterium tuberculosis. Submitted. Articles I, II, III and IV have been reproduced with permission from the respective copyright holders. Additional publications Henriksson L.M., Johansson P., Unge T., Mowbray S.L. (2004). X- ray structure of peptidyl-prolyl cis-trans isomerase A from Mycobac- terium tuberculosis. EJB 271 (20), 4107-4113. Cronin A., Adamska M., Johansson P., Jones T.A., Mowbray S.L., Richter I., Unge T., Arand M. (2005). Characterisation of an epoxide hydrolase from Mycobacterium tuberculosis functionally related to mammalian cholesterol epoxide hydrolase. Naunyn-Schmiedeberg's Arch. Pharmacol. 371(1), R96. Kallas Å.M., Piens K., Denman S.E., Henriksson H., Fäldt J., Jo- hansson P., Brumer H., Teeri T.T. (2005). Enzymatic properties of native and deglycosylated hybrid aspen (Populus tremula x tremu- loides) xyloglucan endotransglycosylase 16A expressed in Pichia pastoris. Biochem. J. 390, 105-113. Contents Inside the Matrix...........................................................................................11 Xyloglucan endotransglycosylases ...............................................................13 Structural studies of a Populus Xyloglucan Endotransglycosylase (Paper I & II)............................................................................................16 Crystallization and structure determination.........................................16 Structure...............................................................................................17 Active site............................................................................................18 A XET-acceptor complex....................................................................19 XET donor binding..............................................................................20 PttXET16A glycosylation....................................................................23 XET transglycosylation .......................................................................24 Conclusions and future perspectives....................................................26 Phasing the unknown ....................................................................................27 Mycobacterium tuberculosis.........................................................................29 The M. tuberculosis genome ....................................................................30 Epoxide hydrolases ..................................................................................30 Structure of M. tuberculosis Rv2740 (Paper III)......................................32 Crystallization and structure determination.........................................32 Structure...............................................................................................33 Active site............................................................................................34 Rv2740 activity and potential substrates .............................................35 Similarities to a human ChEH? ...........................................................36 Conclusions and future perspectives....................................................37 Mtb fatty acid biosynthesis ......................................................................38 Fatty acid ȕ-oxidation...............................................................................39 M. tuberculosis Rv0216 and Rv0130.......................................................41 Structure of M. tuberculosis Rv0216 (Paper IV)......................................41 Crystallization and structure determination.........................................41 Structure...............................................................................................42 Putative active site ...............................................................................43 Putative Rv0216 substrates?................................................................45 Rv0216 a (de)hydratase? .....................................................................46 Related M. tuberculosis proteins .........................................................47 Conclusions and future perspectives....................................................49 Structure of M. tuberculosis Rv0130 (Paper V).......................................50 Crystallization and structure determination.........................................50 Structure...............................................................................................50 Catalytic activity of Rv0130................................................................52 Pockets, prolines and substrate specificity ..........................................53 PHA biosynthesis ................................................................................54 Conclusions and future perspectives....................................................56 Summary in Swedish ....................................................................................57 Acknowledgements.......................................................................................59 References.....................................................................................................61 Abbreviations 3RHDC R-3-hydroxydecanoyl-CoA 4HPC 4-hydroxyphenacyl-CoA ACP Acyl carrier protein ChEH Cholesterol 5,6-oxide hydrolase CoA Coenzyme A CYP Cytochrome P450 mono-oxygenase DHD Double hotdog EGXT Endo-xyloglucan transferase EH Epoxide hydrolase FabA E-hydroxyacyl-ACP dehydratase/isomerase FabD Malonyl-CoA:ACP transacylase FabG E-ketoacyl-ACP reductase FabI 2-trans-enoyl-ACP reductase FabM 2-trans, 3-cis-acyl-ACP isomerase FabZ E-hydroxyacyl-ACP dehydratase FAS Fatty acid synthase system GH Glycoside hydrolase Glc Glucose unit InhA 2-trans-enoyl-ACP reductase KasA / KasB E-ketoacyl-ACP synthase LEH Limonene epoxide hydrolase LTA4 Leukotriene A4 hydrolase MDR Multi drug resistance mEH Microsomal epoxide hydrolase Mtb Mycobacterium tuberculosis NCS Non-crystallographic symmetry PDB Protein Data Bank PHA Polyhydroxyalkanoate PttXET16A Populus tremula x tremuloides XET16A sEH Soluble epoxide hydrolase SeMet Selenomethionine SHD Single hotdog XET Xyloglucan endotransglycosylase XG Xyloglucan XTH Xyloglucan endotransglycosylase/hydrolase Xyl Xylose unit Inside the Matrix Xyloglucan endotransglycosylases Cellulose is by far the most abundant polysaccharide in plants and accounts for 15-90% of the dry mass of primary and secondary cell walls, making it the most abundant biological compound on Earth (Coughlan and Folan, 1979). The cellulose polymer is composed of a non-substituted chain of D- glucose residues, linked by ȕ(1-4) glycosidic bonds. In plants, cellulose forms
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