4u0k: Difference between revisions
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<StructureSection load='4u0k' size='340' side='right' caption='[[4u0k]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4u0k' size='340' side='right' caption='[[4u0k]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4u0k]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2h7n 2h7n]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U0K FirstGlance]. <br> | <table><tr><td colspan='2'>[[4u0k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2h7n 2h7n]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U0K FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=744:(3S)-N-(5-CHLORO-2-METHYLPHENYL)-1-CYCLOHEXYL-5-OXOPYRROLIDINE-3-CARBOXAMIDE'>744</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=744:(3S)-N-(5-CHLORO-2-METHYLPHENYL)-1-CYCLOHEXYL-5-OXOPYRROLIDINE-3-CARBOXAMIDE'>744</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4trj|4trj]], [[4tzk|4tzk]], [[4tzt|4tzt]], [[4u0j|4u0j]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4trj|4trj]], [[4tzk|4tzk]], [[4tzt|4tzt]], [[4u0j|4u0j]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">inhA, Rv1484, MTCY277.05 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=4u0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0k OCA], [http://pdbe.org/4u0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u0k RCSB], [http://www.ebi.ac.uk/pdbsum/4u0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u0k 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=4u0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0k OCA], [http://pdbe.org/4u0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u0k RCSB], [http://www.ebi.ac.uk/pdbsum/4u0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u0k ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4u0k" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4u0k" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Myctu]] | |||
[[Category: Alian, A]] | [[Category: Alian, A]] | ||
[[Category: He, X]] | [[Category: He, X]] | ||
Revision as of 18:03, 15 November 2017
Crystal structure of Mycobacterium tuberculosis enoyl reductase complexed with N-(5-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamideCrystal structure of Mycobacterium tuberculosis enoyl reductase complexed with N-(5-chloro-2-methylphenyl)-1-cyclohexyl-5-oxopyrrolidine-3-carboxamide
Structural highlights
Publication Abstract from PubMedIn view of the worldwide spread of multidrug resistance of Mycobacterium tuberculosis, there is an urgent need to discover antituberculosis agent with novel structures. InhA, the enoyl acyl carrier protein reductase (ENR) from M. tuberculosis, is one of the key enzymes involved in the mycobacterial fatty acid elongation cycle and has been validated as an effective antimicrobial target. We report here the discovery, through high-throughput screening, of a series of pyrrolidine carboxamides as a novel class of potent InhA inhibitors. Crystal structures of InhA complexed with three inhibitors have been used to elucidate the inhibitor binding mode. The potency of the lead compound was improved over 160-fold by subsequent optimization through iterative microtiter library synthesis followed by in situ activity screening without purification. Resolution of racemic mixtures of several inhibitors indicate that only one enantiomer is active as an inhibitor of InhA. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from Mycobacterium tuberculosis.,He X, Alian A, Stroud R, Ortiz de Montellano PR J Med Chem. 2006 Oct 19;49(21):6308-23. PMID:17034137[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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