2nsd
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2nsd.jpg|left|200px]] | [[Image:2nsd.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2nsd", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_2nsd| PDB=2nsd | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Enoyl acyl carrier protein reductase InhA in complex with N-(4-methylbenzoyl)-4-benzylpiperidine''' | '''Enoyl acyl carrier protein reductase InhA in complex with N-(4-methylbenzoyl)-4-benzylpiperidine''' | ||
| Line 23: | Line 20: | ||
==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://www.ncbi.nlm.nih.gov/pubmed/17723305 17723305] | 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: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 29: | Line 25: | ||
[[Category: He, X.]] | [[Category: He, X.]] | ||
[[Category: Montellano, P R.Ortiz de.]] | [[Category: Montellano, P R.Ortiz de.]] | ||
| - | [[Category: | + | [[Category: Enoyl acyl carrier reductase]] |
| - | [[Category: | + | [[Category: Inha]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:51:20 2008'' | |
| - | + | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:51, 4 May 2008
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 Page seeded by OCA on Sun May 4 09:51:20 2008
