How pantothenol intervenes in Coenzyme-A biosynthesis of Mycobacterium tuberculosis

Kumar, Parimal and Chhibber, Manmohan and Surolia, Avadhesha (2007) How pantothenol intervenes in Coenzyme-A biosynthesis of Mycobacterium tuberculosis. In: Biochemical and Biophysical Research Communications, 361 (4). pp. 903-909.

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Abstract

Coenzyme A is an indispensable cofactor for all organisms and holds a central position in a number of pathways. Prokaryotic enzymes involved in the synthesis of CoA are quite different from their mammalian counterparts; hence, they are good targets for the development of antimicrobials to treat many diseases. There are antimicrobials that act by inhibiting CoA biosynthesis. It has been suggested that pantothenol exhibits antibacterial activity by competitively inhibiting pantothenate kinase, a key regulatory enzyme for CoA synthesis. Contrary to these suggestions, in this paper, we demonstrate that pantothenol acts as a substrate for Mycobacterium tuberculosis and Escherichia coli pantothenate kinases. The product, 4'-phosphopantothenol, thus formed inhibits competitively the utilization of 4'-phosphopantothenate by CoaBC. Thus, it is the failure of CoaBC to utilize 4'-phosphopantothenol as a substrate that accounts for the bactericidal activity of pantothenol. (C) 2007 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	Biochemical and Biophysical Research Communications
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	Pantothenol; Pantothenate kinase; Coenzyme A; Isothermal titration calorimetry; Mycobacterium tuberculosis; 4′-Phosphopantothenate; Pantothenate
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	19 May 2010 04:40
Last Modified:	19 Sep 2010 06:01
URI:	http://eprints.iisc.ac.in/id/eprint/27467

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