5vrl
From Proteopedia
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<StructureSection load='5vrl' size='340' side='right' caption='[[5vrl]], [[Resolution|resolution]] 2.65Å' scene=''> | <StructureSection load='5vrl' size='340' side='right' caption='[[5vrl]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5vrl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VRL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vrl]] is a 1 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=5VRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VRL FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JA:(~{N}~{E})-~{N}-[[2-[[2-ethylsulfonyl-1,1-bis(oxidanyl)-3,4-dihydro-2,3,1$l^{4}-benzodiazaborinin-7-yl]oxy]-5-(trifluoromethyl)phenyl]methylidene]hydroxylamine'>9JA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JA:(~{N}~{E})-~{N}-[[2-[[2-ethylsulfonyl-1,1-bis(oxidanyl)-3,4-dihydro-2,3,1$l^{4}-benzodiazaborinin-7-yl]oxy]-5-(trifluoromethyl)phenyl]methylidene]hydroxylamine'>9JA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vrn|5vrn]], [[5vrm|5vrm]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vrn|5vrn]], [[5vrm|5vrm]]</td></tr> | ||
| + | <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> | ||
<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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vrl OCA], [http://pdbe.org/5vrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vrl RCSB], [http://www.ebi.ac.uk/pdbsum/5vrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vrl 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=5vrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vrl OCA], [http://pdbe.org/5vrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vrl RCSB], [http://www.ebi.ac.uk/pdbsum/5vrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vrl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| + | |||
| + | 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> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5vrl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Mycto]] | ||
[[Category: Abendroth, J]] | [[Category: Abendroth, J]] | ||
[[Category: Edwards, T E]] | [[Category: Edwards, T E]] | ||
Revision as of 06:58, 5 December 2018
CRYSTAL STRUCTURE OF THE INHA FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH AN12855, EBSI 4333.
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