View source for 3bli


==Crystal structure of the catalytic domain of LiCMS in complexed with pyruvate and acetyl-CoA==
<StructureSection load='3bli' size='340' side='right'caption='[[3bli]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bli]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leptospira_interrogans Leptospira interrogans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bli OCA], [https://pdbe.org/3bli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bli RCSB], [https://www.ebi.ac.uk/pdbsum/3bli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bli ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CIMA_LEPIN CIMA_LEPIN] Catalyzes the condensation of pyruvate and acetyl-coenzyme A to form (R)-citramalate (PubMed:15292141, PubMed:18498255, PubMed:19351325). Shows strict substrate specificity for pyruvate. Cannot use alpha-ketoisovalerate, alpha-ketobutyrate, alpha-ketoisocaproate, alpha-ketoglutarate or glyoxylate (PubMed:15292141, PubMed:18498255).<ref>PMID:15292141</ref> <ref>PMID:18498255</ref> <ref>PMID:19351325</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3bli_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bli ConSurf].
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== Publication Abstract from PubMed ==
Leptospira interrogans is the causative agent for leptospirosis, a zoonotic disease of global importance. In contrast with most other micro-organisms, L. interrogans employs a pyruvate pathway to synthesize isoleucine and LiCMS (L. interrogans citramalate synthase) catalyses the first reaction of the pathway which converts pyruvate and acetyl-CoA into citramalate, thus making it an attractive target for the development of antibacterial agents. We report here the crystal structures of the catalytic domain of LiCMS and its complexes with substrates, and kinetic and mutagenesis studies of LiCMS, which together reveal the molecular basis of the high substrate specificity and the catalytic mechanism of LiCMS. The catalytic domain consists of a TIM barrel flanked by an extended C-terminal region. It forms a homodimer in the crystal structure, and the active site is located at the centre of the TIM barrel near the C-terminal ends of the beta-strands and is composed of conserved residues of the beta-strands of one subunit and the C-terminal region of the other. The substrate specificity of LiCMS towards pyruvate against other alpha-oxo acids is dictated primarily by residues Leu(81), Leu(104) and Tyr(144), which form a hydrophobic pocket to accommodate the C(2)-methyl group of pyruvate. The catalysis follows the typical aldol condensation reaction, in which Glu(146) functions as a catalytic base to activate the methyl group of acetyl-CoA to form an enolated acetyl-CoA intermediate and Arg(16) as a general acid to stabilize the intermediate.

Molecular basis of the substrate specificity and the catalytic mechanism of citramalate synthase from Leptospira interrogans.,Ma J, Zhang P, Zhang Z, Zha M, Xu H, Zhao G, Ding J Biochem J. 2008 Oct 1;415(1):45-56. PMID:18498255<ref>PMID:18498255</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3bli" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leptospira interrogans]]
[[Category: Ma J]]
[[Category: Zhang P]]