3kx7: Difference between revisions
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==Structural basis of the activity and substrate specificity of the fluoroacetyl-CoA FlK - apo wild type FlK== | ==Structural basis of the activity and substrate specificity of the fluoroacetyl-CoA FlK - apo wild type FlK== | ||
<StructureSection load='3kx7' size='340' side='right' caption='[[3kx7]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='3kx7' size='340' side='right' caption='[[3kx7]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3kx7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3kx7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"streptomyces_cattleya"_kahan_et_al._1979 "streptomyces cattleya" kahan et al. 1979]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KX7 FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kuv|3kuv]], [[3kuw|3kuw]], [[3kv7|3kv7]], [[3kv8|3kv8]], [[3kvi|3kvi]], [[3kvu|3kvu]], [[3kvz|3kvz]], [[3kw1|3kw1]], [[3kx8|3kx8]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kuv|3kuv]], [[3kuw|3kuw]], [[3kv7|3kv7]], [[3kv8|3kv8]], [[3kvi|3kvi]], [[3kvu|3kvu]], [[3kvz|3kvz]], [[3kw1|3kw1]], [[3kx8|3kx8]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">flK, fluoroacetyl-CoA thioesterase FlK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29303 Streptomyces cattleya])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">flK, fluoroacetyl-CoA thioesterase FlK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29303 "Streptomyces cattleya" Kahan et al. 1979])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kx7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kx7 RCSB], [http://www.ebi.ac.uk/pdbsum/3kx7 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kx7 OCA], [http://pdbe.org/3kx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kx7 RCSB], [http://www.ebi.ac.uk/pdbsum/3kx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kx7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ | [[http://www.uniprot.org/uniprot/FLK_STRCT FLK_STRCT]] Hydrolyzes fluoroacetyl-CoA before it can react with citrate synthase, and thus confers fluoroacetate resistance. Can not use acetyl-CoA as substrate.<ref>PMID:16720268</ref> <ref>PMID:20836570</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</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/ | </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=3kx7 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3kx7" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Streptomyces cattleya]] | [[Category: Streptomyces cattleya kahan et al. 1979]] | ||
[[Category: Blundell, T L]] | [[Category: Blundell, T L]] | ||
[[Category: Chirgadze, D Y]] | [[Category: Chirgadze, D Y]] | ||
Revision as of 03:31, 5 August 2016
Structural basis of the activity and substrate specificity of the fluoroacetyl-CoA FlK - apo wild type FlKStructural basis of the activity and substrate specificity of the fluoroacetyl-CoA FlK - apo wild type FlK
Structural highlights
Function[FLK_STRCT] Hydrolyzes fluoroacetyl-CoA before it can react with citrate synthase, and thus confers fluoroacetate resistance. Can not use acetyl-CoA as substrate.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe thioesterase FlK from the fluoroacetate-producing Streptomyces cattleya catalyzes the hydrolysis of fluoroacetyl-coenzyme A. This provides an effective self-defense mechanism, preventing any fluoroacetyl-coenzyme A formed from being further metabolized to 4-hydroxy-trans-aconitate, a lethal inhibitor of the tricarboxylic acid cycle. Remarkably, FlK does not accept acetyl-coenzyme A as a substrate. Crystal structure analysis shows that FlK forms a dimer, in which each subunit adopts a hot dog fold as observed for type II thioesterases. Unlike other type II thioesterases, which invariably utilize either an aspartate or a glutamate as catalytic base, we show by site-directed mutagenesis and crystallography that FlK employs a catalytic triad composed of Thr(42), His(76), and a water molecule, analogous to the Ser/Cys-His-acid triad of type I thioesterases. Structural comparison of FlK complexed with various substrate analogues suggests that the interaction between the fluorine of the substrate and the side chain of Arg(120) located opposite to the catalytic triad is essential for correct coordination of the substrate at the active site and therefore accounts for the substrate specificity. Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK.,Dias MV, Huang F, Chirgadze DY, Tosin M, Spiteller D, Dry EF, Leadlay PF, Spencer JB, Blundell TL J Biol Chem. 2010 Jul 16;285(29):22495-504. Epub 2010 Apr 29. PMID:20430898[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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