2qnx

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Revision as of 05:40, 7 May 2008

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Template:STRUCTURE 2qnx

Crystal structure of the complex between the mycobacterium beta-ketoacyl-acyl carrier protein synthase III (FABH) and 11-[(decyloxycarbonyl)dithio]-undecanoic acid

Overview

Mycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C(16)-C(22)) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an "open" form during substrate binding and product release, and a "closed" form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors.

About this Structure

2QNX is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH., Sachdeva S, Musayev FN, Alhamadsheh MM, Scarsdale JN, Wright HT, Reynolds KA, Chem Biol. 2008 Apr;15(4):402-12. PMID:18420147 Page seeded by OCA on Wed May 7 08:40:49 2008