Molecular Mechanism of the site-specific self-cleavage of the RNA phosphodiester backbone by a Twister Ribozyme
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Altres documents de l'autoria: Świderek, Katarzyna; Martí Forés, Sergio; Tuñón, Iñaki; Moliner, Vicent; Bertrán, Juan
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Mostra el registre complet de l'elementcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
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Molecular Mechanism of the site-specific self-cleavage of the RNA phosphodiester backbone by a Twister RibozymeData de publicació
2017-02Editor
SpringerCita bibliogràfica
ŚWIDEREK, 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.Tipus de document
info:eu-repo/semantics/articleVersió de l'editorial
https://link.springer.com/article/10.1007/s00214-017-2060-8Versió
info:eu-repo/semantics/updatedVersionParaules clau / Matèries
Resum
The 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 ... [+]
The 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. [-]
Descripció
Published as part of the special collection of articles derived
from the 10th Congress on Electronic Structure: Principles and
Applications (ESPA-2016).
Proyecto de investigación
Spanish 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)Drets d'accés
© The Author(s) 2017
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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