2eft

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spinqualitylabelsall models PDB ID 2eft Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.00Å
Ligands:	, ,
Gene:	fabH (Escherichia coli)
Activity:	Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41
Related:	2GYO, 1HND, 1EBL
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Methanethiol-CYS 112 inhibition complex of E. coli ketoacyl synthase III (FABH) and Coenzyme A (high concentration (1.7mM) soak)

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 C1 to C10 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

2EFT is a Single protein structure of sequence from Escherichia coli. 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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