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2gyo
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | The first step of the reaction catalyzed by the homodimeric FabH from a | + | 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== | ==About this Structure== | ||
| Line 10: | Line 10: | ||
==Reference== | ==Reference== | ||
| - | Alkyl-CoA | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17524982 17524982] |
[[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | [[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Alhamadsheh, M | + | [[Category: Alhamadsheh, M M.]] |
[[Category: Florova, G.]] | [[Category: Florova, G.]] | ||
| - | [[Category: Komissarov, A | + | [[Category: Komissarov, A A.]] |
[[Category: Musayev, F.]] | [[Category: Musayev, F.]] | ||
| - | [[Category: Reynolds, K | + | [[Category: Reynolds, K A.]] |
[[Category: Sachdeva, S.]] | [[Category: Sachdeva, S.]] | ||
[[Category: Scarsdale, N.]] | [[Category: Scarsdale, N.]] | ||
| - | [[Category: Wright, H | + | [[Category: Wright, H T.]] |
[[Category: COA]] | [[Category: COA]] | ||
[[Category: MEE]] | [[Category: MEE]] | ||
| Line 30: | Line 30: | ||
[[Category: mycobacterium tuberculosis]] | [[Category: mycobacterium tuberculosis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:36:25 2008'' |
Revision as of 15:36, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 17:36:25 2008
Categories: 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. | COA | MEE | SO4 | Alkyl-coa-disulfide | Fatty acid biosynthesis | Mechanism-based inhibitor | Mycobacterium tuberculosis
