2nsd
From Proteopedia
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|PDB= 2nsd |SIZE=350|CAPTION= <scene name='initialview01'>2nsd</scene>, resolution 1.9Å | |PDB= 2nsd |SIZE=350|CAPTION= <scene name='initialview01'>2nsd</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=4PI:N-(4-METHYLBENZOYL)-4-BENZYLPIPERIDINE'>4PI</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> |
| - | |ACTIVITY= [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] | + | |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> |
|GENE= inhA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | |GENE= inhA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2h7i|2H7I]], [[2h7l|2H7L]], [[2h7m|2H7M]], [[2h7n|2H7N]], [[2h7p|2H7P]], [[1p45|1P45]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsd OCA], [http://www.ebi.ac.uk/pdbsum/2nsd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nsd RCSB]</span> | ||
}} | }} | ||
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[[Category: He, X.]] | [[Category: He, X.]] | ||
[[Category: Montellano, P R.Ortiz de.]] | [[Category: Montellano, P R.Ortiz de.]] | ||
| - | [[Category: 4PI]] | ||
| - | [[Category: NAD]] | ||
[[Category: enoyl acyl carrier reductase]] | [[Category: enoyl acyl carrier reductase]] | ||
[[Category: inha]] | [[Category: inha]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:07:37 2008'' |
Revision as of 01:07, 31 March 2008
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| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | inhA (Mycobacterium tuberculosis) | ||||||
| Activity: | [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 | ||||||
| Related: | 2H7I, 2H7L, 2H7M, 2H7N, 2H7P, 1P45
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Enoyl acyl carrier protein reductase InhA in complex with N-(4-methylbenzoyl)-4-benzylpiperidine
Overview
InhA, the enoyl acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis, is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. We report here the discovery, through high-throughput screening, of a series of arylamides as a novel class of potent InhA inhibitors. These direct InhA inhibitors require no mycobacterial enzymatic activation and thus circumvent the resistance mechanism to antitubercular prodrugs such as INH and ETA that is most commonly observed in drug-resistant clinical isolates. The crystal structure of InhA complexed with one representative inhibitor reveals the binding mode of the inhibitor within the InhA active site. Further optimization through a microtiter synthesis strategy followed by in situ activity screening led to the discovery of a potent InhA inhibitor with in vitro IC(50)=90 nM, representing a 34-fold potency improvement over the lead compound.
About this Structure
2NSD is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides., He X, Alian A, Ortiz de Montellano PR, Bioorg Med Chem. 2007 Nov 1;15(21):6649-58. Epub 2007 Aug 15. PMID:17723305 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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