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dc.contributor.authorMorillas, Montserrat
dc.contributor.authorGómez-Puertas, Paulino
dc.contributor.authorBentebibel, Assia
dc.contributor.authorSellés, Eva
dc.contributor.authorCasals i Farré, Núria
dc.contributor.authorValencia, Alfonso
dc.contributor.authorHegardt, Fausto G.
dc.contributor.authorAsins, Guillermina
dc.contributor.authorSerra, Dolors
dc.date.accessioned2021-05-05T15:15:30Z
dc.date.available2021-05-05T15:15:30Z
dc.date.issued2003-03-14
dc.identifier.citationMorillas, Montserrat; Gómez-Puertas, Paulino; Bentebibel, Assia [et al.]. Identification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibition. Journal of Biological Chemistry, 2003, 278(11), p. 9058-9063. Disponible en: <https://www.sciencedirect.com/science/article/pii/S0021925819712745?via%3Dihub>. Fecha de acceso: 5 may. 2021. DOI: 10.1074/jbc.M209999200ca
dc.identifier.issn0021-9258ca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/2520
dc.description.abstractCarnitine palmitoyltransferase (CPT) I, which catalyzes the conversion of palmitoyl-CoA to palmitoylcarnitine facilitating its transport through the mitochondrial membranes, is inhibited by malonyl-CoA. By using the SequenceSpace algorithm program to identify amino acids that participate in malonyl-CoA inhibition in all carnitine acyltransferases, we found 5 conserved amino acids (Thr314, Asn464, Ala478, Met593, and Cys608, rat liver CPT I coordinates) common to inhibitable malonyl-CoA acyltransferases (carnitine octanoyltransferase and CPT I), and absent in noninhibitable malonyl-CoA acyltransferases (CPT II, carnitine acetyltransferase (CAT) and choline acetyltransferase (ChAT)). To determine the role of these amino acid residues in malonyl-CoA inhibition, we prepared the quintuple mutant CPT I T314S/N464D/A478G/M593S/C608A as well as five single mutants CPT I T314S, N464D, A478G, M593S, and C608A. In each case the CPT I amino acid selected was mutated to that present in the same homologous position in CPT II, CAT, and ChAT. Because mutant M593S nearly abolished the sensitivity to malonyl-CoA, two other Met593mutants were prepared: M593A and M593E. The catalytic efficiency (V max/K m) of CPT I in mutants A478G and C608A and all Met593 mutants toward carnitine as substrate was clearly increased. In those CPT I proteins in which Met593 had been mutated, the malonyl-CoA sensitivity was nearly abolished. Mutations in Ala478, Cys608, and Thr314 to their homologous amino acid residues in CPT II, CAT, and ChAT caused various decreases in malonyl-CoA sensitivity. Ala478 is located in the structural model of CPT I near the catalytic site and participates in the binding of malonyl-CoA in the low affinity site (Morillas, M., Gómez-Puertas, P., Rubı́, B., Clotet, J., Ariño, J., Valencia, A., Hegardt, F. G., Serra, D., and Asins, G. (2002) J. Biol. Chem. 277, 11473–11480). Met593 may participate in the interaction of malonyl-CoA in the second affinity site, whose location has not been reported.en
dc.format.extent6ca
dc.language.isoengca
dc.publisherAmerican Society for Biochemistry and Molecular Biologyca
dc.relation.ispartofJournal of Biological Chemistryca
dc.relation.ispartofseries278;11
dc.rightsUnder a Creative Commons license. This is an Open Access article under theCC BY license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.otherMutació (Biologia)ca
dc.subject.otherMitocondrisca
dc.subject.otherEnzimsca
dc.subject.otherMetabolisme -- Trastornsca
dc.subject.otherAminoàcids -- Metabolismeca
dc.subject.otherMutación (Biología)es
dc.subject.otherMitocondriases
dc.subject.otherEnzimases
dc.subject.otherMetabolismo -- Trastornoses
dc.subject.otherAminoácidos -- Metabolismoes
dc.subject.otherMutation (Biology)en
dc.subject.otherMitochondriaen
dc.subject.otherEnzymesen
dc.subject.otherMetabolism -- Disordersen
dc.subject.otherAmino acids -- Metabolismen
dc.titleIdentification of conserved amino acid residues in rat liver carnitine palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of methionine 593 abolishes malonyl-CoA inhibitionen
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/publishedVersionca
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PN/ES/1PN/BMC2001-3048ca
dc.subject.udc57ca
dc.subject.udc61ca
dc.identifier.doihttps://dx.doi.org/10.1074/jbc.M209999200ca


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Under a Creative Commons license. This is an Open Access article under theCC BY license.
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