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==Crystal structure of InhA(S94A) mutant in complex with pyridomycin== | |||
<StructureSection load='4bge' size='340' side='right' caption='[[4bge]], [[Resolution|resolution]] 2.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4bge]] is a 6 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=4BGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BGE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PYW:PYRIDOMYCIN'>PYW</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bgi|4bgi]]</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=4bge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bge OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bge RCSB], [http://www.ebi.ac.uk/pdbsum/4bge PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a-kind binding mode that discloses a new means of InhA inhibition. Proof-of-principle studies show how structure-assisted drug design can improve the activity of new pyridomycin derivatives. | |||
Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA.,Hartkoorn RC, Pojer F, Read JA, Gingell H, Neres J, Horlacher OP, Altmann KH, Cole ST Nat Chem Biol. 2013 Dec 1. doi: 10.1038/nchembio.1405. PMID:24292073<ref>PMID:24292073</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
==See Also== | |||
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Cole, S T | [[Category: Cole, S T]] | ||
[[Category: Hartkoorn, R C | [[Category: Hartkoorn, R C]] | ||
[[Category: Pojer, F | [[Category: Pojer, F]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 21:42, 21 December 2014
Crystal structure of InhA(S94A) mutant in complex with pyridomycinCrystal structure of InhA(S94A) mutant in complex with pyridomycin
Structural highlights
Publication Abstract from PubMedPyridomycin, a natural product with potent antituberculosis activity, inhibits a major drug target, the InhA enoyl reductase. Here, we unveil the co-crystal structure and unique ability of pyridomycin to block both the NADH cofactor- and lipid substrate-binding pockets of InhA. This is to our knowledge a first-of-a-kind binding mode that discloses a new means of InhA inhibition. Proof-of-principle studies show how structure-assisted drug design can improve the activity of new pyridomycin derivatives. Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA.,Hartkoorn RC, Pojer F, Read JA, Gingell H, Neres J, Horlacher OP, Altmann KH, Cole ST Nat Chem Biol. 2013 Dec 1. doi: 10.1038/nchembio.1405. PMID:24292073[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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