2nsd
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2nsd.jpg|left|200px]] | + | [[Image:2nsd.jpg|left|200px]] |
| - | + | ||
| - | '''Enoyl acyl carrier protein reductase InhA in complex with N-(4-methylbenzoyl)-4-benzylpiperidine''' | + | {{Structure |
| + | |PDB= 2nsd |SIZE=350|CAPTION= <scene name='initialview01'>2nsd</scene>, resolution 1.9Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> and <scene name='pdbligand=4PI:N-(4-METHYLBENZOYL)-4-BENZYLPIPERIDINE'>4PI</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] | ||
| + | |GENE= inhA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | }} | ||
| + | |||
| + | '''Enoyl acyl carrier protein reductase InhA in complex with N-(4-methylbenzoyl)-4-benzylpiperidine''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2NSD is a [ | + | 2NSD 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=2NSD OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17723305 17723305] |
[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]] | [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
| Line 24: | Line 33: | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:50:29 2008'' |
Revision as of 15:50, 20 March 2008
| |||||||
| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | inhA (Mycobacterium tuberculosis) | ||||||
| Activity: | [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 | ||||||
| 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)]]
Page seeded by OCA on Thu Mar 20 17:50:29 2008
