2gyo | pdb_00002gyo

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

File:2gyo.jpg

spinqualitylabelsall models 2gyo, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

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 SO4, COA and MEE 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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