2qx1

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Template:STRUCTURE 2qx1

Crystal structure of the complex between mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FABH) and decyl-COA disulfide

Overview

The dimeric Mycobacterium tuberculosis FabH (mtFabH) catalyses a Claisen-type condensation between an acyl-CoA and malonyl-acyl carrier protein (ACP) to initiate the Type II fatty acid synthase cycle. To analyze the initial covalent acylation of mtFabH with acyl-CoA, we challenged it with mixture of C(6)-C(20) acyl-CoAs and the ESI-MS analysis showed reaction at both subunits and a strict specificity for C(12) acyl CoA. Crystallographic and ESI-MS studies of mtFabH with a decyl-CoA disulfide inhibitor revealed a decyl chain bound in acyl-binding channels of both subunits through disulfide linkage to the active site cysteine. These data provide the first unequivocal evidence that both subunits of mtFabH can react with substrates or inhibitor. The discrepancy between the observed C(12) acyl-CoA substrate specificity in the initial acylation step and the higher catalytic efficiency of mtFabH for C(18)-C(20) acyl-CoA substrates in the overall mtFabH catalyzed reaction suggests a role for M. tuberculosis ACP as a specificity determinant in this reaction.

About this Structure

2QX1 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Probing reactivity and substrate specificity of both subunits of the dimeric Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA substrates., Sachdeva S, Musayev F, Alhamadsheh MM, Neel Scarsdale J, Tonie Wright H, Reynolds KA, Bioorg Chem. 2008 Apr;36(2):85-90. Epub 2007 Dec 21. PMID:18096200 Page seeded by OCA on Sun May 4 15:51:19 2008