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2gyo

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[[Image:2gyo.jpg|left|200px]]
[[Image:2gyo.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2gyo |SIZE=350|CAPTION= <scene name='initialview01'>2gyo</scene>, resolution 2.00&Aring;
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The line below this paragraph, containing "STRUCTURE_2gyo", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MEE:METHANETHIOL'>MEE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= fabH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
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-->
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|DOMAIN=
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{{STRUCTURE_2gyo| PDB=2gyo | SCENE= }}
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|RELATEDENTRY=[[1hnd|1HND]], [[1ebl|1EBL]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gyo OCA], [http://www.ebi.ac.uk/pdbsum/2gyo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gyo RCSB]</span>
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}}
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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.]]
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[[Category: alkyl-coa-disulfide]]
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[[Category: Alkyl-coa-disulfide]]
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[[Category: fatty acid biosynthesis]]
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[[Category: Fatty acid biosynthesis]]
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[[Category: mechanism-based inhibitor]]
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[[Category: Mechanism-based inhibitor]]
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[[Category: mycobacterium tuberculosis]]
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[[Category: Mycobacterium tuberculosis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:39:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:23:04 2008''
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Revision as of 02:39, 4 May 2008

Template:STRUCTURE 2gyo

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

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