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| | <StructureSection load='3kvu' size='340' side='right'caption='[[3kvu]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3kvu' size='340' side='right'caption='[[3kvu]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kvu]] is a 4 chain structure with sequence from [https://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=3KVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kvu]] is a 4 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=3KVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KVU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3kuv|3kuv]], [[3kuw|3kuw]], [[3kv7|3kv7]], [[3kv8|3kv8]], [[3kvi|3kvi]], [[3kvz|3kvz]], [[3kw1|3kw1]], [[3kx7|3kx7]], [[3kx8|3kx8]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">flK, fluoroacetyl-CoA thioesterase FlK ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3kvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kvu OCA], [https://pdbe.org/3kvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kvu RCSB], [https://www.ebi.ac.uk/pdbsum/3kvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kvu ProSAT]</span></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=3kvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kvu OCA], [https://pdbe.org/3kvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kvu RCSB], [https://www.ebi.ac.uk/pdbsum/3kvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kvu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Streptomyces cattleya kahan et al. 1979]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Streptomyces cattleya]] |
| - | [[Category: Chirgadze, D Y]] | + | [[Category: Blundell TL]] |
| - | [[Category: Dias, M V.B]] | + | [[Category: Chirgadze DY]] |
| - | [[Category: Huang, F]] | + | [[Category: Dias MVB]] |
| - | [[Category: Leadlay, P F]] | + | [[Category: Huang F]] |
| - | [[Category: Spencer, J B]] | + | [[Category: Leadlay PF]] |
| - | [[Category: Spiteller, D]] | + | [[Category: Spencer JB]] |
| - | [[Category: Tosin, M]] | + | [[Category: Spiteller D]] |
| - | [[Category: Valentine, E F]] | + | [[Category: Tosin M]] |
| - | [[Category: Fluoroacetyl-coa thioesterase flk]]
| + | [[Category: Valentine EF]] |
| - | [[Category: Hot-dog folding]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Thioesterase]]
| + | |
| 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 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang F, Haydock SF, Spiteller D, Mironenko T, Li TL, O'Hagan D, Leadlay PF, Spencer JB. The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A. Chem Biol. 2006 May;13(5):475-84. PMID:16720268 doi:http://dx.doi.org/S1074-5521(06)00084-6
- ↑ Weeks AM, Coyle SM, Jinek M, Doudna JA, Chang MC. Structural and Biochemical Studies of a Fluoroacetyl-CoA-Specific Thioesterase Reveal a Molecular Basis for Fluorine Selectivity. Biochemistry. 2010 Oct 11. PMID:20836570 doi:10.1021/bi101102u
- ↑ Dias MV, Huang F, Chirgadze DY, Tosin M, Spiteller D, Dry EF, Leadlay PF, Spencer JB, Blundell TL. Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK. J Biol Chem. 2010 Jul 16;285(29):22495-504. Epub 2010 Apr 29. PMID:20430898 doi:10.1074/jbc.M110.107177
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