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| | <StructureSection load='5w3k' size='340' side='right'caption='[[5w3k]], [[Resolution|resolution]] 1.59Å' scene=''> | | <StructureSection load='5w3k' size='340' side='right'caption='[[5w3k]], [[Resolution|resolution]] 1.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w3k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w3k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W3K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9TY:cyclopropane-1,1-dicarboxylic+acid'>9TY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.589Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ilvC, BMF23_13825, BO217_1422, ERS072840_02559 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9TY:cyclopropane-1,1-dicarboxylic+acid'>9TY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </span></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=5w3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3k OCA], [https://pdbe.org/5w3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w3k RCSB], [https://www.ebi.ac.uk/pdbsum/5w3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3k ProSAT]</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=5w3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w3k OCA], [http://pdbe.org/5w3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w3k RCSB], [http://www.ebi.ac.uk/pdbsum/5w3k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w3k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A145BYP4_STAAU A0A145BYP4_STAAU]] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435][SAAS:SAAS00826005] | + | [https://www.uniprot.org/uniprot/ILVC_STAA8 ILVC_STAA8] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ketol-acid reductoisomerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Guddat, L W]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Kandale, A]] | + | [[Category: Guddat LW]] |
| - | [[Category: McGeary, R P]] | + | [[Category: Kandale A]] |
| - | [[Category: Patel, K M]] | + | [[Category: McGeary RP]] |
| - | [[Category: Schembri, M]] | + | [[Category: Patel KM]] |
| - | [[Category: Schenk, G]] | + | [[Category: Schembri M]] |
| - | [[Category: Teran, D]] | + | [[Category: Schenk G]] |
| - | [[Category: Zheng, S]] | + | [[Category: Teran D]] |
| - | [[Category: Isomerase]]
| + | [[Category: Zheng S]] |
| - | [[Category: Ketol-acid reductisomerase]]
| + | |
| Structural highlights
Function
ILVC_STAA8 Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435]
Publication Abstract from PubMed
Ketol-acid reductoisomerase (KARI) is an NAD(P)H and Mg2+-dependent enzyme of the branched-chain amino acid (BCAA) biosynthesis pathway. Here we describe the first crystal structures of Staphylococcus aureus (Sa) KARI, these in complex with two transition state analogs, cyclopropane-1,1-dicarboxylate (CPD) and N-isopropyloxalyl hydroxamate (IpOHA). These compounds bind competitively and in multi-dentate manner to KARI with Ki values of 2.73 muM and 7.9 nM, respectively; however, IpOHA binds slowly to the enzyme. Interestingly, intact IpOHA is present in only ~25% of binding sites, while its deoxygenated form is present in the remaining sites. This deoxy form of IpOHA binds rapidly to Sa KARI, but with much weaker affinity (Ki = 21 muM). Thus, our data pinpoint the origin of the slow binding mechanism of IpOHA. Furthermore, we propose that CPD mimics the early stage of the catalytic reaction (preceding the reduction step), while IpOHA mimics the late stage (after the reduction took place). These structural insights will guide strategies to design potent and rapidly binding derivatives of these compound for the development of novel biocides.
Crystal structures of Staphylococcus aureus ketol-acid reductoisomerase in complex with two transition state analogs that have biocidal activity.,Patel K, Teran D, Zheng S, Kandale A, Garcia M, Lv Y, Schembri MA, McGeary RP, Schenk G, Guddat LW Chemistry. 2017 Oct 4. doi: 10.1002/chem.201704481. PMID:28975665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Patel K, Teran D, Zheng S, Kandale A, Garcia M, Lv Y, Schembri MA, McGeary RP, Schenk G, Guddat LW. Crystal structures of Staphylococcus aureus ketol-acid reductoisomerase in complex with two transition state analogs that have biocidal activity. Chemistry. 2017 Oct 4. doi: 10.1002/chem.201704481. PMID:28975665 doi:http://dx.doi.org/10.1002/chem.201704481
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