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| | <StructureSection load='4ypo' size='340' side='right'caption='[[4ypo]], [[Resolution|resolution]] 1.00Å' scene=''> | | <StructureSection load='4ypo' size='340' side='right'caption='[[4ypo]], [[Resolution|resolution]] 1.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ypo]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YPO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ypo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YPO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ilvC, IQ45_13380, IU12_14180, IU13_13535, IU21_13700, T209_13330 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=4ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypo OCA], [https://pdbe.org/4ypo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ypo RCSB], [https://www.ebi.ac.uk/pdbsum/4ypo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypo 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/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ypo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypo OCA], [http://pdbe.org/4ypo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ypo RCSB], [http://www.ebi.ac.uk/pdbsum/4ypo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ILVC_MYCTU ILVC_MYCTU] 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. It is also able to use 3-hydroxypyruvate (HP).<ref>PMID:26876563</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ketol-acid reductoisomerase|Ketol-acid reductoisomerase]] | + | *[[Ketol-acid reductoisomerase 3D structures|Ketol-acid reductoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ketol-acid reductoisomerase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Guddat, L W]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Lv, Y]] | + | [[Category: Guddat LW]] |
| - | [[Category: Branch chain amino acid]] | + | [[Category: Lv Y]] |
| - | [[Category: Ilvc]]
| + | |
| - | [[Category: Knotted protein]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| Structural highlights
Function
ILVC_MYCTU 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. It is also able to use 3-hydroxypyruvate (HP).[1]
Publication Abstract from PubMed
The biosynthetic pathway for the branched-chain amino acids is present in plants, fungi and bacteria, but not in animals, making it an attractive target for herbicidal and antimicrobial drug discovery. Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) is the second enzyme in this pathway, converting in a Mg2+ - and NADPH-dependent reaction either 2-acetolactate or 2-aceto-2-hydroxybutyrate to their corresponding 2,3-dihydroxy-3-alkylbutyrate products. Here, we have determined the crystal structure of Mycobacterium tuberculosis KARI (Mt KARI), a class I KARI, with two magnesium ions bound in the active site. X-ray data were obtained to 1.0 A resolution and the final model has an Rfree of 0.174. The structure shows that the active site is solvent-accessible with the two metal ions separated by 4.7 A. A comparison of this structure with that of Mg2+ -free Pseudomonas aeruginosa KARI suggests that upon magnesium binding no movement of the N-domain relative to the C-domain occurs. However, upon formation of the Michaelis complex, as illustrated in the structure of Slackia exigua KARI in complex with NADH.Mg2+ .N-hydroxy-N-isopropyloxamate (IpOHA, a transition state analog), domain movements and reduction of the metal-metal distance to 3.5 A are observed. This inherent flexibility therefore appears to be critical for initiation of the KARI-catalyzed reaction. This study provides new insights into the complex structural rearrangements required for activity of KARIs, particularly those belonging to class I, and provides the framework for the rational design of Mt KARI inhibitors that can be tested as novel antituberculosis agents. This article is protected by copyright. All rights reserved.
Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution: A potential target for anti-tuberculosis drug discovery.,Lv Y, Kandale A, Wun SJ, McGeary RP, Williams SJ, Kobe B, Sieber V, Schembri MA, Schenk G, Guddat LW FEBS J. 2016 Feb 15. doi: 10.1111/febs.13672. PMID:26876563[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lv Y, Kandale A, Wun SJ, McGeary RP, Williams SJ, Kobe B, Sieber V, Schembri MA, Schenk G, Guddat LW. Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution: A potential target for anti-tuberculosis drug discovery. FEBS J. 2016 Feb 15. doi: 10.1111/febs.13672. PMID:26876563 doi:http://dx.doi.org/10.1111/febs.13672
- ↑ Lv Y, Kandale A, Wun SJ, McGeary RP, Williams SJ, Kobe B, Sieber V, Schembri MA, Schenk G, Guddat LW. Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution: A potential target for anti-tuberculosis drug discovery. FEBS J. 2016 Feb 15. doi: 10.1111/febs.13672. PMID:26876563 doi:http://dx.doi.org/10.1111/febs.13672
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