2gyo: Difference between revisions
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'''Methanethiol-Cys 112 Inhibition Complex of E. Coli Ketoacyl Synthase III (FabH) and Coenzyme A''' | '''Methanethiol-Cys 112 Inhibition Complex of E. Coli Ketoacyl Synthase III (FabH) and Coenzyme A''' | ||
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[[Category: Scarsdale, N.]] | [[Category: Scarsdale, N.]] | ||
[[Category: Wright, H T.]] | [[Category: Wright, H T.]] | ||
[[Category: | [[Category: Alkyl-coa-disulfide]] | ||
[[Category: | [[Category: Fatty acid biosynthesis]] | ||
[[Category: | [[Category: Mechanism-based inhibitor]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:39:36 2008'' | |||
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Revision as of 02:39, 4 May 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 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
2GYO 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 Page seeded by OCA on Sun May 4 05:39:36 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Beta-ketoacyl-acyl-carrier-protein synthase I
- Escherichia coli
- Single protein
- Alhamadsheh, M M.
- Florova, G.
- Komissarov, A A.
- Musayev, F.
- Reynolds, K A.
- Sachdeva, S.
- Scarsdale, N.
- Wright, H T.
- Alkyl-coa-disulfide
- Fatty acid biosynthesis
- Mechanism-based inhibitor
- Mycobacterium tuberculosis
