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| - | [[Image:2h7m.jpg|left|200px]] | + | #REDIRECT [[4tzk]] This PDB entry is obsolete and replaced by 4tzk |
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| - | {{Structure
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| - | |PDB= 2h7m |SIZE=350|CAPTION= <scene name='initialview01'>2h7m</scene>, resolution 1.62Å
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| - | |SITE=
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| - | |LIGAND= <scene name='pdbligand=641:(3S)-1-CYCLOHEXYL-N-(3,5-DICHLOROPHENYL)-5-OXOPYRROLIDINE-3-CARBOXAMIDE'>641</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>
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| - | |ACTIVITY= <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>
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| - | |GENE= inhA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
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| - | |DOMAIN=
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| - | |RELATEDENTRY=[[1eny|1ENY]], [[1p45|1P45]], [[1enz|1ENZ]], [[2b35|2B35]], [[2b36|2B36]], [[1bvr|1BVR]]
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| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7m OCA], [http://www.ebi.ac.uk/pdbsum/2h7m PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h7m RCSB]</span>
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| - | }}
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| - | '''Crystal structure of Mycobacterium tuberculosis enoyl reductase (InhA) complexed with 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide'''
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| - | ==Overview==
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| - | In 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.
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| - | ==About this Structure==
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| - | 2H7M is a [[Single protein]] structure of 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=2H7M OCA].
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| - | ==Reference==
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| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17034137 17034137]
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| - | [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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| - | [[Category: Mycobacterium tuberculosis]]
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| - | [[Category: Single protein]]
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| - | [[Category: Alian, A.]]
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| - | [[Category: He, X.]]
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| - | [[Category: Montellano, P R.Ortiz de.]]
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| - | [[Category: Stroud, R.]]
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| - | [[Category: enoyl acyl carrier reductase]]
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| - | [[Category: inha]]
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| - | [[Category: oxidoreductase]]
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| - | [[Category: pyrrolidine carboxamide]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:26:37 2008''
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