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dc.contributor.authorŚwiderek, Katarzyna
dc.contributor.authorTuñón, Iñaki
dc.contributor.authorWilliams, Ian H.
dc.contributor.authorMoliner, Vicent
dc.date.accessioned2018-06-11T10:24:09Z
dc.date.available2018-06-11T10:24:09Z
dc.date.issued2018-02
dc.identifier.citationŚWIDEREK, Katarzyna, et al. Insights on the Origin of Catalysis on Glycine N-Methyltransferase from Computational Modeling. Journal of the American Chemical Society, 2018, 140.12: 4327-4334.ca_CA
dc.identifier.urihttp://hdl.handle.net/10234/175089
dc.description.abstractThe origin of enzyme catalysis remains a question of debate despite much intense study. We report a QM/MM theoretical study of the SN2 methyl transfer reaction catalyzed by a glycine N-methyltransferase (GNMT) and three mutants to test whether recent experimental observations of rate-constant reductions and variations in inverse secondary α-3H kinetic isotope effects (KIEs) should be attributed to changes in the methyl donor−acceptor distance (DAD): is catalysis due to a compression effect? Semiempirical (AM1) and DFT (M06-2X) methods were used to describe the QM subset of atoms, while OPLS-AA and TIP3P classical force fields were used for the protein and water molecules, respectively. The computed activation free energies and KIEs are in good agreement with experimental data, but the mutations do not meaningfully affect the DAD: compression cannot explain the experimental variations on KIEs. On the contrary, electrostatic properties in the active site correlate with the catalytic activity of wild type and mutants. The plasticity of the enzyme moderates the effects of the mutations, explaining the rather small degree of variation in KIEs and reactivities.ca_CA
dc.format.extent7 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherAmerican Chemical Societyca_CA
dc.rightsCopyright © 2018 American Chemical Societyca_CA
dc.subjectenzyme catalysisca_CA
dc.subjectQM/MMca_CA
dc.titleInsights on the Origin of Catalysis on Glycine N-Methyltransferase from Computational Modelingca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttps://doi.org/10.1021/jacs.7b13655
dc.relation.projectIDpanish Ministerio de Economi ́ a y Competitividad and FEDER funds (project CTQ2015-66223-C2), Generalitat Valenciana (PROME- TEOII/2014/022), Universitat Jaume I (project UJI · B2017- 31), and the USA National Institute of Health (ref No. NIH R01 GM065368) ; Spanish Ministerio de Educación Cultura y Deporte for travel financial support (project PRX17/00166)ca_CA
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttps://pubs.acs.org/doi/abs/10.1021/jacs.7b13655ca_CA
dc.type.versioninfo:eu-repo/semantics/submittedVersionca_CA


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