2gyo

From Proteopedia

Revision as of 13:00, 23 January 2008

Methanethiol-Cys 112 Inhibition Complex of E. Coli Ketoacyl Synthase III (FabH) and Coenzyme A

Overview

The first step of the reaction catalyzed by the homodimeric FabH from a, dissociated fatty acid synthase is acyl transfer from acyl-CoA to an, active site cysteine. We report that C(1) to C(10) alkyl-CoA disulfides, irreversibly inhibit Escherichia coli FabH (ecFabH) and Mycobacterium, tuberculosis FabH with relative efficiencies that reflect these enzymes', differential acyl-group specificity. Crystallographic and kinetic studies, with MeSSCoA show rapid inhibition of one monomer of ecFabH through, formation of a methyl disulfide conjugate with this cysteine. Reaction of, the second subunit with either MeSSCoA or acetyl-CoA is much slower. In, the presence of malonyl-ACP, the acylation rate of the second subunit is, restored to that of the native ecFabH. These observations suggest a, catalytic model in which a structurally disordered apo-ecFabH dimer orders, on binding either the first substrate, acetyl-CoA, or the inhibitor, MeSSCoA, and is restored to a disordered state on binding of malonyl-ACP.

About this Structure

2GYO is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Full crystallographic information is available from OCA.

Reference

Alkyl-CoA Disulfides as Inhibitors and Mechanistic Probes for FabH Enzymes., Alhamadsheh MM, Musayev F, Komissarov AA, Sachdeva S, Wright HT, Scarsdale N, Florova G, Reynolds KA, Chem Biol. 2007 May;14(5):513-24. PMID:17524982

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