Structural highlights
Function
INHA_MYCTU
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ He X, Alian A, Ortiz de Montellano PR. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. Bioorg Med Chem. 2007 Nov 1;15(21):6649-58. Epub 2007 Aug 15. PMID:17723305 doi:10.1016/j.bmc.2007.08.013