3kv8: Difference between revisions
New page: '''Unreleased structure''' The entry 3kv8 is ON HOLD Authors: Dias, M.V.B., Huang, F., Chirgadze, D.Y., Tosin, M., Spiteller, D, Valentine, E.F., Leadlay, P.F., Spencer, J.B., Blundell,... |
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The | ==Structural basis of the activity and substrate specificity of the fluoroacetyl-CoA thioesterase FlK - Wild type FlK in complex with fluoro-acetate== | ||
<StructureSection load='3kv8' size='340' side='right'caption='[[3kv8]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3kv8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_cattleya Streptomyces cattleya]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KV8 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAH:FLUOROACETIC+ACID'>FAH</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kv8 OCA], [https://pdbe.org/3kv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kv8 RCSB], [https://www.ebi.ac.uk/pdbsum/3kv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kv8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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 == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/3kv8_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=3kv8 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:20430898</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3kv8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thioesterase 3D structures|Thioesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces cattleya]] | |||
[[Category: Blundell TL]] | |||
[[Category: Chirgadze DY]] | |||
[[Category: Dias MVB]] | |||
[[Category: Huang F]] | |||
[[Category: Leadlay PF]] | |||
[[Category: Spencer JB]] | |||
[[Category: Spiteller D]] | |||
[[Category: Tosin M]] | |||
[[Category: Valentine EF]] | |||
Latest revision as of 12:21, 30 October 2024
Structural basis of the activity and substrate specificity of the fluoroacetyl-CoA thioesterase FlK - Wild type FlK in complex with fluoro-acetateStructural basis of the activity and substrate specificity of the fluoroacetyl-CoA thioesterase FlK - Wild type FlK in complex with fluoro-acetate
Structural highlights
FunctionFLK_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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