2eft

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(New page: 200px<br /><applet load="2eft" size="450" color="white" frame="true" align="right" spinBox="true" caption="2eft, resolution 2.00&Aring;" /> '''Methanethiol-CYS 112...)
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[[Image:2eft.jpg|left|200px]]<br /><applet load="2eft" size="450" color="white" frame="true" align="right" spinBox="true"
 
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'''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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==Overview==
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==Methanethiol-CYS 112 inhibition complex of E. coli ketoacyl synthase III (FABH) and Coenzyme A (high concentration (1.7mM) soak)==
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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.
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<StructureSection load='2eft' size='340' side='right'caption='[[2eft]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2eft]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EFT FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MEE:METHANETHIOL'>MEE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2eft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eft OCA], [https://pdbe.org/2eft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2eft RCSB], [https://www.ebi.ac.uk/pdbsum/2eft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2eft ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FABH_ECOLI FABH_ECOLI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain.[HAMAP-Rule:MF_01815]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ef/2eft_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2eft ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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<ref>PMID:17524982</ref>
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2EFT OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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]
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</div>
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[[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]]
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<div class="pdbe-citations 2eft" style="background-color:#fffaf0;"></div>
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[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Alhamadsheh, M.M.]]
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[[Category: Florova, G.]]
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[[Category: Komissarov, A.A.]]
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[[Category: Musayev, F.]]
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[[Category: Reynolds, K.A.]]
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[[Category: Sachdeva, S.]]
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[[Category: Scarsdale, N.]]
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[[Category: Wright, H.T.]]
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[[Category: COA]]
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[[Category: MEE]]
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[[Category: SO4]]
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[[Category: alkyl-coa-disulfide]]
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[[Category: e. coli]]
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[[Category: fatty acid biosynthesis]]
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[[Category: half sites occupancy]]
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[[Category: mechanism-based inhibitor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:01:43 2007''
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==See Also==
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*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli]]
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[[Category: Large Structures]]
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[[Category: Alhamadsheh MM]]
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[[Category: Florova G]]
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[[Category: Komissarov AA]]
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[[Category: Musayev F]]
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[[Category: Reynolds KA]]
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[[Category: Sachdeva S]]
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[[Category: Scarsdale N]]
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[[Category: Wright HT]]

Current revision

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

PDB ID 2eft

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