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dc.contributor.authorCasals Farré, Núria
dc.contributor.authorGómez-Puertas, Paulino
dc.contributor.authorPié, Juan
dc.contributor.authorMir, Cecilia
dc.contributor.authorRoca, Ramón
dc.contributor.authorPuisac, Beatriz
dc.contributor.authorAledo, Rosa
dc.contributor.authorClotet, Josep
dc.contributor.authorMenao, Sebastián
dc.contributor.authorSerra, Dolors
dc.contributor.authorAsins, Guillermina
dc.contributor.authorTill, Jacqueline
dc.contributor.authorElias-Jones, Alun C.
dc.contributor.authorCresto, Juan C.
dc.contributor.authorChamoles, Nestor A.
dc.contributor.authorAbdenur, Jose E.
dc.contributor.authorMayatepek, Ertan
dc.contributor.authorBesley, Guy
dc.contributor.authorValencia, Alfonso
dc.contributor.authorHegardt, Fausto G.
dc.date.accessioned2020-05-26T07:58:54Z
dc.date.available2020-05-26T07:58:54Z
dc.date.issued2003
dc.identifier.citationCasals Farré, Núria; Gómez-Puertas, Paulino; Pié, Juan [et al.]. Structural (betaalpha) 8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase. Journal of Biological Chemistry, 2003, 278(31), p. 29016-29023. Disponible en: <https://www.jbc.org/content/278/31/29016>. Fecha de acceso: 26 may. 2020. DOI: 10.1074/jbc.M304276200.ca
dc.identifier.issn1083-351Xca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/1547
dc.description.abstractThis study describes three novel homozygous missense mutations (S75R, S201Y, and D204N) in the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase gene, which caused 3-hydroxy-3-methylglutaric aciduria in patients from Germany, England, and Argentina. Expression studies in Escherichia coli show that S75R and S201Y substitutions completely abolished the HMG-CoA lyase activity, whereas D204N reduced catalytic efficiency to 6.6% of the wild type. We also propose a three-dimensional model for human HMG-CoA lyase containing a (βα)8 (TIM) barrel structure. The model is supported by the similarity with analogous TIM barrel structures of functionally related proteins, by the localization of catalytic amino acids at the active site, and by the coincidence between the shape of the substrate (HMG-CoA) and the predicted inner cavity. The three novel mutations explain the lack of HMG-CoA lyase activity on the basis of the proposed structure: in S75R and S201Y because the new amino acid residues occlude the substrate cavity, and in D204N because the mutation alters the electrochemical environment of the active site. We also report the localization of all missense mutations reported to date and show that these mutations are located in the β-sheets around the substrate cavity.ca
dc.format.extent34ca
dc.language.isoengca
dc.publisherAmerican Society for Biochemistry and Molecular Biologyca
dc.relation.ispartofJournal of Biological Chemistryca
dc.relation.ispartofseries278;31
dc.rights© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.ca
dc.subject.otherAminoàcidsca
dc.subject.otherMutació (Biologia)
dc.subject.otherEnzims
dc.subject.otherMetabolisme
dc.subject.otherProteïnes
dc.subject.otherAminoácidos
dc.subject.otherMutación (Biología)
dc.subject.otherEnzimas
dc.subject.otherMetabolismo
dc.subject.otherProteínas
dc.subject.otherAmino acids
dc.subject.otherMutation (Biology)
dc.subject.otherEnzymes
dc.subject.otherMetabolism
dc.subject.otherProteins
dc.titleStructural (betaalpha) 8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyaseca
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/acceptedVersionca
dc.embargo.termscapca
dc.subject.udc61ca
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M304276200ca


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