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dc.contributor.authorŚwiderek, Katarzyna
dc.contributor.authorMartí Forés, Sergio
dc.contributor.authorTuñón, Iñaki
dc.contributor.authorMoliner, Vicent
dc.contributor.authorBertrán, Juan
dc.date.accessioned2017-12-15T11:08:49Z
dc.date.available2017-12-15T11:08:49Z
dc.date.issued2017-02
dc.identifier.citationŚWIDEREK, Katarzyna, et al. Molecular mechanism of the site-specific self-cleavage of the RNA phosphodiester backbone by a twister ribozyme. Theoretical Chemistry Accounts, 2017, vol. 136, no 3, p. 31.ca_CA
dc.identifier.urihttp://hdl.handle.net/10234/171012
dc.descriptionPublished as part of the special collection of articles derived from the 10th Congress on Electronic Structure: Principles and Applications (ESPA-2016).ca_CA
dc.description.abstractThe catalytic activity of some classes of natural RNA, named as ribozymes, has been discovered just in the past decades. In this paper, the cleavage of the RNA phosphodiester backbone has been studied in aqueous solution and in a twister ribozyme from Oryza sativa. The free energy profiles associated with a baseline substrate-assisted mechanism for the reaction in the enzyme and in solution were computed by means of free energy perturbation methods within hybrid QM/MM potentials, describing the chemical system by the M06-2× functional and the environment by means of the AMBER and TIP3P force fields. The results confirm that this is a stepwise mechanism kinetically controlled by the second step that involves the P–O5′ breaking bond concomitant with the proton transfer from the OP1 atom to the leaving O5′ atom. 18O kinetic isotope effects on the nucleophile and leaving oxygen atoms, in very good agreement with experiments, also support this description. Nevertheless, the free energy profiles in the enzyme and in solution are almost coincident which, despite that the rate-limiting activation free energy is in very good agreement with experimental data of counterpart reactions in solution, rule out this substrate-assisted catalysis mechanism for the twister ribozyme from O. sativa. Catalysis must come from the role of alternative acid–base species not available in aqueous solution, but the rate-limiting transition state must be associated with the P–O5′ bond cleavage.ca_CA
dc.format.extent11 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherSpringerca_CA
dc.rights© The Author(s) 2017ca_CA
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/4.0/*
dc.subjecttwister ribozymeca_CA
dc.subjectreaction mechanismca_CA
dc.subjectQM/MMca_CA
dc.subjectfree energy profilesca_CA
dc.subjectKIEsca_CA
dc.titleMolecular Mechanism of the site-specific self-cleavage of the RNA phosphodiester backbone by a Twister Ribozymeca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1007/s00214-017-2060-8
dc.relation.projectIDSpanish Ministerio de Economía y Competitividad (CTQ2015-66223-C2) ; Universitat Jaume I (project P1•1B2014-26) ; Generalitat Valenciana (PROMETEOII/2014/022) ; Polish Ministry of Science and Higher Education (“Iuventus Plus” programme project no. 0478/IP3/2015/73, 2015-2016)ca_CA
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttps://link.springer.com/article/10.1007/s00214-017-2060-8ca_CA
dc.type.versioninfo:eu-repo/semantics/updatedVersionca_CA


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