4dre: Difference between revisions
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==Mycobacterium tuberculosis InhA in complex with NADH== | |||
===Mycobacterium tuberculosis | <StructureSection load='4dre' size='340' side='right' caption='[[4dre]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dre]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dqu|4dqu]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inhA, MT1531, MTCY277.05, Rv1484 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</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=4dre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dre OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dre RCSB], [http://www.ebi.ac.uk/pdbsum/4dre PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an important source of antibiotics including potent anti-tuberculosis agents. Here, we describe pyridomycin, a compound produced by Dactylosporangium fulvum with specific cidal activity against mycobacteria. By selecting pyridomycin-resistant mutants of Mycobacterium tuberculosis, whole-genome sequencing and genetic validation, we identified the NADH-dependent enoyl- (Acyl-Carrier-Protein) reductase InhA as the principal target and demonstrate that pyridomycin inhibits mycolic acid synthesis in M. tuberculosis. Furthermore, biochemical and structural studies show that pyridomycin inhibits InhA directly as a competitive inhibitor of the NADH-binding site, thereby identifying a new, druggable pocket in InhA. Importantly, the most frequently encountered isoniazid-resistant clinical isolates remain fully susceptible to pyridomycin, thus opening new avenues for drug development. -->See accompanying article http://dx.doi.org/10.1002/emmm.201201811. | |||
Towards a new tuberculosis drug: pyridomycin - nature's isoniazid.,Hartkoorn RC, Sala C, Neres J, Pojer F, Magnet S, Mukherjee R, Uplekar S, Boy-Rottger S, Altmann KH, Cole ST EMBO Mol Med. 2012 Sep 17. doi: 10.1002/emmm.201201689. PMID:22987724<ref>PMID:22987724</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Boy, S | [[Category: Boy, S]] | ||
[[Category: Cole, S T | [[Category: Cole, S T]] | ||
[[Category: Hartkoorn, R C | [[Category: Hartkoorn, R C]] | ||
[[Category: Pojer, F | [[Category: Pojer, F]] | ||
[[Category: Enoyl-acp reductase]] | [[Category: Enoyl-acp reductase]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 11:45, 21 December 2014
Mycobacterium tuberculosis InhA in complex with NADH
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