title: Structure-based design of a novel class of potent inhibitors of InhA, the enoyl acyl carrier protein reductase from Mycobacterium tuberculosis: a computer modelling approach.
abstract: The NADH-dependent Enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis has been shown to be the primary target of the frontline drug isoniazid (INH). However, INH must be first activated by katG gene, mutations in which have mediated resistance to INH. Recently, direct inhibitors of InhA have been reported. Using a structure-based approach, we have identified a tripeptide inhibitor with the sequence WYW, which is 100 times more potent than the existing inhibitors. It is therefore, a potential lead compound for the development of new anti-TB drugs.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India. gitasubba@gmail.com
authors.forename: Gita
authors.initials: G
authors.lastname: Subba Rao
authors.forename: Rajakrishnan
authors.initials: R
authors.lastname: Vijayakrishnan
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D015195:Drug Design; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010455:Peptides; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); C085257:InhA protein, Mycobacterium