Phosphorylation of the Mycobacterium tuberculosis β-ketoacyl-ACP reductase MabA regulates mycolic acid biosynthesis
نویسندگان
چکیده
Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Universités de Montpellier II et I, CNRS; UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. Institut de Biologie et Chimie des Protéines (IBCP UMR 5086), CNRS, Université Lyon1, IFR128 BioSciences, Lyon-Gerland, 7 passage du Vercors, 69367 Lyon Cedex 07, France. Institut National de la Santé et de la Recherche Médicale, U554, 34090 Montpellier, France Centre de Biochimie Structurale, Unité Mixte de Recherche 5048, Centre National de la Recherche Scientifique, Université Montpellier I & II, 34093 Montpellier, France INSERM, DIMNP, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
منابع مشابه
The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance.
A target of the anti-tuberculosis drugs isoniazid (INH) and ethionamide (ETH) has been shown to be an enoyl reductase, encoded by the inhA gene. The mabA (mycolic acid biosynthesis A) gene is located immediately upstream of inhA in Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium smegmatis. The MabA protein from M. tuberculosis was expressed in Escherichia coli and shown to hav...
متن کاملIn vitro inhibition of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein reductase MabA by isoniazid.
The first-line specific antituberculous drug isoniazid inhibits the fatty acid elongation system (FAS) FAS-II involved in the biosynthesis of mycolic acids, which are major lipids of the mycobacterial envelope. The MabA protein that catalyzes the second step of the FAS-II elongation cycle is structurally and functionally related to the in vivo target of isoniazid, InhA, an NADH-dependent enoyl-...
متن کاملThe Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III activity is inhibited by phosphorylation on a single threonine residue.
Mycolic acids are hallmark features of the Mycobacterium tuberculosis cell wall. They are synthesized by the condensation of two fatty acids, a C56-64-meromycolyl chain and a C24-26-fatty acyl chain. Meromycolates are produced via the combination of type I and type II fatty acid synthases (FAS-I and FAS-II). The beta-ketoacyl-acyl carrier protein (ACP) synthase III (mtFabH) links FAS-I and FAS-...
متن کاملPlatensimycin Activity against Mycobacterial β-Ketoacyl-ACP Synthases
BACKGROUND There is an urgent need for the discovery and development of new drugs against Mycobacterium tuberculosis, the causative agent of tuberculosis, especially due to the recent emergence of multi-drug and extensively-drug resistant strains. Herein, we have examined the susceptibility of mycobacteria to the natural product platensimycin. METHODS AND FINDINGS We have demonstrated that pl...
متن کاملMycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis.
Mycolic acids consist of long-chain alpha-alkyl-beta-hydroxy fatty acids that are produced by successive rounds of elongation catalysed by a type II fatty acid synthase (FAS-II). A key feature in the elongation process is the condensation of a two-carbon unit from malonyl-acyl-carrier protein (ACP) to a growing acyl-ACP chain catalysed by a beta-ketoacyl-ACP synthase (Kas). In the present study...
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تاریخ انتشار 2010