2eft
From Proteopedia
(New page: 200px<br /><applet load="2eft" size="450" color="white" frame="true" align="right" spinBox="true" caption="2eft, resolution 2.00Å" /> '''Methanethiol-CYS 112...) |
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| - | [[Image:2eft.jpg|left|200px]]<br /><applet load="2eft" size=" | + | [[Image:2eft.jpg|left|200px]]<br /><applet load="2eft" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2eft, resolution 2.00Å" /> | caption="2eft, resolution 2.00Å" /> | ||
'''Methanethiol-CYS 112 inhibition complex of E. coli ketoacyl synthase III (FABH) and Coenzyme A (high concentration (1.7mM) soak)'''<br /> | '''Methanethiol-CYS 112 inhibition complex of E. coli ketoacyl synthase III (FABH) and Coenzyme A (high concentration (1.7mM) soak)'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2EFT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4, COA and MEE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] Full crystallographic information is available from [http:// | + | 2EFT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=COA:'>COA</scene> and <scene name='pdbligand=MEE:'>MEE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EFT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: mechanism-based inhibitor]] | [[Category: mechanism-based inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:54:10 2008'' |
Revision as of 12:54, 23 January 2008
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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 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
2EFT 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 Wed Jan 23 14:54:10 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 | E. coli | Fatty acid biosynthesis | Half sites occupancy | Mechanism-based inhibitor
