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| | ==Crystal structure of the regulatory domain of LiCMS in complexed with isoleucine - type II== | | ==Crystal structure of the regulatory domain of LiCMS in complexed with isoleucine - type II== |
| - | <StructureSection load='3f6g' size='340' side='right' caption='[[3f6g]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3f6g' size='340' side='right'caption='[[3f6g]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f6g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"leptospira_icteroides"_noguchi_1919 "leptospira icteroides" noguchi 1919]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f6g]] is a 2 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=3F6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F6G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ILE:ISOLEUCINE'>ILE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ble|3ble]], [[3blf|3blf]], [[3bli|3bli]], [[3f6h|3f6h]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ILE:ISOLEUCINE'>ILE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cimA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=173 "Leptospira icteroides" Noguchi 1919])</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=3f6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6g OCA], [https://pdbe.org/3f6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f6g RCSB], [https://www.ebi.ac.uk/pdbsum/3f6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6g ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(R)-citramalate_synthase (R)-citramalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.182 2.3.1.182] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3f6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f6g OCA], [http://pdbe.org/3f6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f6g RCSB], [http://www.ebi.ac.uk/pdbsum/3f6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f6g ProSAT]</span></td></tr> | + | |
| | </table> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6g_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f6g_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3f6g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3f6g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[2-isopropylmalate synthase 3D structures|2-isopropylmalate synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Leptospira icteroides noguchi 1919]] | + | [[Category: Large Structures]] |
| - | [[Category: Ding, J]] | + | [[Category: Leptospira interrogans]] |
| - | [[Category: Ma, J]] | + | [[Category: Ding J]] |
| - | [[Category: Zhang, P]] | + | [[Category: Ma J]] |
| - | [[Category: Zhao, G]] | + | [[Category: Zhang P]] |
| - | [[Category: Acyltransferase]]
| + | [[Category: Zhao G]] |
| - | [[Category: Allosteric regulation]]
| + | |
| - | [[Category: Feedback inhibition]]
| + | |
| - | [[Category: Licmsc]]
| + | |
| - | [[Category: Selectivity]]
| + | |
| - | [[Category: Specificity]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
LiCMS (Leptospira interrogans citramalate synthase) catalyses the first reaction of the isoleucine biosynthesis pathway in L. interrogans, the pathogen of leptospirosis. The catalytic reaction is regulated through feedback inhibition by its end product isoleucine. To understand the molecular basis of the high selectivity of the inhibitor and the mechanism of feedback inhibition, we determined the crystal structure of LiCMSC (C-terminal regulatory domain of LiCMS) in complex with isoleucine, and performed a biochemical study of the inhibition of LiCMS using mutagenesis and kinetic methods. LiCMSC forms a dimer of dimers in both the crystal structure and solution and the dimeric LiCMSC is the basic functional unit. LiCMSC consists of six beta-strands forming two anti-parallel beta-sheets and two alpha-helices and assumes a betaalphabeta three-layer sandwich structure. The inhibitor isoleucine is bound in a pocket at the dimer interface and has both hydrophobic and hydrogen-bonding interactions with several conserved residues of both subunits. The high selectivity of LiCMS for isoleucine over leucine is primarily dictated by the residues, Tyr430, Leu451, Tyr454, Ile458 and Val468, that form a hydrophobic pocket to accommodate the side chain of the inhibitor. The binding of isoleucine has inhibitory effects on the binding of both the substrate, pyruvate, and coenzyme, acetyl-CoA, in a typical pattern of K-type inhibition. The structural and biochemical data from the present study together suggest that the binding of isoleucine affects the binding of the substrate and coenzyme at the active site, possibly via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction.
Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans.,Zhang P, Ma J, Zhang Z, Zha M, Xu H, Zhao G, Ding J Biochem J. 2009 Jun 12;421(1):133-43. PMID:19351325[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xu H, Zhang Y, Guo X, Ren S, Staempfli AA, Chiao J, Jiang W, Zhao G. Isoleucine biosynthesis in Leptospira interrogans serotype lai strain 56601 proceeds via a threonine-independent pathway. J Bacteriol. 2004 Aug;186(16):5400-9. PMID:15292141 doi:10.1128/JB.186.16.5400-5409.2004
- ↑ Ma J, Zhang P, Zhang Z, Zha M, Xu H, Zhao G, Ding J. Molecular basis of the substrate specificity and the catalytic mechanism of citramalate synthase from Leptospira interrogans. Biochem J. 2008 Oct 1;415(1):45-56. PMID:18498255 doi:http://dx.doi.org/10.1042/BJ20080242
- ↑ Zhang P, Ma J, Zhang Z, Zha M, Xu H, Zhao G, Ding J. Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans. Biochem J. 2009 Jun 12;421(1):133-43. PMID:19351325 doi:10.1042/BJ20090336
- ↑ Zhang P, Ma J, Zhang Z, Zha M, Xu H, Zhao G, Ding J. Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans. Biochem J. 2009 Jun 12;421(1):133-43. PMID:19351325 doi:10.1042/BJ20090336
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