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Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK

Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK

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DIAS, Marcio V. B., Fanglu HUANG, Dimitri Y. CHIRGADZE, Manuela TOSIN, Dieter SPITELLER, Emily F. V. DRY, Peter F. LEADLAY, Jonathan B. SPENCER, Tom L. BLUNDELL, 2010. Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK. In: Journal of Biological Chemistry. 285(29), pp. 22495-22504. ISSN 0021-9258. eISSN 1083-351X

@article{Dias2010-07-16Struc-15288, title={Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK}, year={2010}, doi={10.1074/jbc.M110.107177}, number={29}, volume={285}, issn={0021-9258}, journal={Journal of Biological Chemistry}, pages={22495--22504}, author={Dias, Marcio V. B. and Huang, Fanglu and Chirgadze, Dimitri Y. and Tosin, Manuela and Spiteller, Dieter and Dry, Emily F. V. and Leadlay, Peter F. and Spencer, Jonathan B. and Blundell, Tom L.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/15288"> <dc:rights>deposit-license</dc:rights> <dc:contributor>Blundell, Tom L.</dc:contributor> <dc:creator>Dry, Emily F. V.</dc:creator> <dc:contributor>Dias, Marcio V. B.</dc:contributor> <dc:creator>Blundell, Tom L.</dc:creator> <dc:creator>Dias, Marcio V. B.</dc:creator> <dc:contributor>Tosin, Manuela</dc:contributor> <dc:contributor>Spiteller, Dieter</dc:contributor> <dcterms:abstract xml:lang="eng">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 Thr42, His76, 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 Arg120 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.</dcterms:abstract> <dc:contributor>Dry, Emily F. V.</dc:contributor> <dc:creator>Tosin, Manuela</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Spencer, Jonathan B.</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/15288"/> <dc:contributor>Leadlay, Peter F.</dc:contributor> <dc:creator>Huang, Fanglu</dc:creator> <dc:creator>Spiteller, Dieter</dc:creator> <dcterms:bibliographicCitation>Publ. in: The Journal of Biological Chemistry ; 285 (2010), 29. - pp. 22495-22504</dcterms:bibliographicCitation> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-10-19T07:27:55Z</dc:date> <dcterms:title>Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK</dcterms:title> <dc:creator>Leadlay, Peter F.</dc:creator> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dc:contributor>Chirgadze, Dimitri Y.</dc:contributor> <dcterms:issued>2010-07-16</dcterms:issued> <dc:creator>Spencer, Jonathan B.</dc:creator> <dc:creator>Chirgadze, Dimitri Y.</dc:creator> <dc:contributor>Huang, Fanglu</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-10-19T07:27:55Z</dcterms:available> </rdf:Description> </rdf:RDF>

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