Double-Metal-Ion/Single-Metal-Ion Mechanisms of the Cleavage Reaction of Ribozymes: First-Principles Molecular Dynamics Simulations of a Fully Hydrated Model System.
J Chem Theory Comput
; 1(5): 925-34, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-26641908
ABSTRACT
The role of metal cations (Mg(2+)) in the cleavage reaction of fully hydrated RNA enzymes is investigated via Car-Parrinello calculations. We find that the action of two metal catalysts is the most efficient way to promote, on one hand, the proton abstraction from O(2)(')-H that triggers the nucleophilic attack and, on the other hand, the weakening and subsequent cleavage of the P-O(5)(') bond. The elimination of one of the two metal cations is shown to lead to an increase in the activation energy. Furthermore, we also find that an OH(-) included in the coordination shell of the Mg(2+) close to O(2)(') promotes the initial proton abstraction and prevents its transfer to the ribozyme in both single- and double-metal-ion pathways, consistently with the experiment. This suggests that in real ribozyme systems, the double-metal-ion reaction mechanism in the presence of an OH(-) anion is favored with respect to single-metal-ion mechanisms.
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01-internacional
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MEDLINE
Idioma:
En
Ano de publicação:
2005
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Article