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| | ==Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct== | | ==Mycobacterium tuberculosis InhA (S94A) bound with INH-NAD adduct== |
| - | <StructureSection load='2nv6' size='340' side='right' caption='[[2nv6]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2nv6' size='340' side='right'caption='[[2nv6]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nv6]] is a 1 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=2NV6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NV6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nv6]] is a 1 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=2NV6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NV6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE+DINUCLEOTIDE'>ZID</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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inhA ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE+DINUCLEOTIDE'>ZID</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=2nv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nv6 OCA], [https://pdbe.org/2nv6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nv6 RCSB], [https://www.ebi.ac.uk/pdbsum/2nv6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nv6 ProSAT], [https://www.topsan.org/Proteins/TBSGC/2nv6 TOPSAN]</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=2nv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nv6 OCA], [http://pdbe.org/2nv6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nv6 RCSB], [http://www.ebi.ac.uk/pdbsum/2nv6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nv6 ProSAT], [http://www.topsan.org/Proteins/TBSGC/2nv6 TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | + | *[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Sacchettini, J C]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, F]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Inha]] | + | [[Category: Sacchettini JC]] |
| - | [[Category: Isoniazid]] | + | [[Category: Wang F]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: S94a]]
| + | |
| - | [[Category: Tuberculosis]]
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| Structural highlights
Function
INHA_MYCTU
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
Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.
Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid.,Vilcheze C, Wang F, Arai M, Hazbon MH, Colangeli R, Kremer L, Weisbrod TR, Alland D, Sacchettini JC, Jacobs WR Jr Nat Med. 2006 Sep;12(9):1027-9. Epub 2006 Aug 13. PMID:16906155[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vilcheze C, Wang F, Arai M, Hazbon MH, Colangeli R, Kremer L, Weisbrod TR, Alland D, Sacchettini JC, Jacobs WR Jr. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat Med. 2006 Sep;12(9):1027-9. Epub 2006 Aug 13. PMID:16906155 doi:10.1038/nm1466
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