5vrm

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==CRYSTAL STRUCTURE OF THE INHA FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH AN12855, EBSI 4333.==
==CRYSTAL STRUCTURE OF THE INHA FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH AN12855, EBSI 4333.==
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<StructureSection load='5vrm' size='340' side='right' caption='[[5vrm]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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<StructureSection load='5vrm' size='340' side='right'caption='[[5vrm]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5vrm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VRM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VRM FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5vrm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VRM FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JJ:[[(2~{R},3~{S},4~{R},5~{R})-5-(3-aminocarbonylpyridin-1-ium-1-yl)-3-oxidanyl-4-[[1-oxidanyl-6-[4-(trifluoromethyl)phenoxy]-3~{H}-2,1$l^{4}-benzoxaborol-1-yl]oxy]oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+hydrogen+phosphate'>9JJ</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vrn|5vrn]], [[5vrl|5vrl]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9JJ:[[(2~{R},3~{S},4~{R},5~{R})-5-(3-aminocarbonylpyridin-1-ium-1-yl)-3-oxidanyl-4-[[1-oxidanyl-6-[4-(trifluoromethyl)phenoxy]-3~{H}-2,1$l^{4}-benzoxaborol-1-yl]oxy]oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+hydrogen+phosphate'>9JJ</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inhA, MT1531 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5vrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vrm OCA], [https://pdbe.org/5vrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vrm RCSB], [https://www.ebi.ac.uk/pdbsum/5vrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vrm ProSAT]</span></td></tr>
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<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>
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<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=5vrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vrm OCA], [http://pdbe.org/5vrm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vrm RCSB], [http://www.ebi.ac.uk/pdbsum/5vrm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vrm ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]
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New antitubercular agents are needed to combat the spread of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis. The frontline antitubercular drug isoniazid (INH) targets the mycobacterial enoyl-ACP reductase, InhA. Resistance to INH is predominantly through mutations affecting the prodrug-activating enzyme KatG. Here, we report the identification of the diazaborines as a new class of direct InhA inhibitors. The lead compound, AN12855, exhibited in vitro bactericidal activity against replicating bacteria and was active against several drug-resistant clinical isolates. Biophysical and structural investigations revealed that AN12855 binds to and inhibits the substrate-binding site of InhA in a cofactor-independent manner. AN12855 showed good drug exposure after i.v. and oral delivery, with 53% oral bioavailability. Delivered orally, AN12855 exhibited dose-dependent efficacy in both an acute and chronic murine model of tuberculosis infection that was comparable with INH. Combined, AN12855 is a promising candidate for the development of new antitubercular agents.
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Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA.,Xia Y, Zhou Y, Carter DS, McNeil MB, Choi W, Halladay J, Berry PW, Mao W, Hernandez V, O'Malley T, Korkegian A, Sunde B, Flint L, Woolhiser LK, Scherman MS, Gruppo V, Hastings C, Robertson GT, Ioerger TR, Sacchettini J, Tonge PJ, Lenaerts AJ, Parish T, Alley M Life Sci Alliance. 2018 Jun 1;1(3):e201800025. doi: 10.26508/lsa.201800025., eCollection 2018 Jun. PMID:30456352<ref>PMID:30456352</ref>
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==See Also==
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*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5vrm" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Mycto]]
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[[Category: Large Structures]]
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[[Category: Abendroth, J]]
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[[Category: Mycobacterium tuberculosis CDC1551]]
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[[Category: Edwards, T E]]
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[[Category: Abendroth J]]
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[[Category: Lorimer, D]]
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[[Category: Edwards TE]]
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[[Category: Enoyl-acyl reductase]]
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[[Category: Lorimer D]]
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[[Category: Inha]]
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[[Category: Oxidoreductase]]
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[[Category: Tuberculosis]]
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Current revision

CRYSTAL STRUCTURE OF THE INHA FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH AN12855, EBSI 4333.

PDB ID 5vrm

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