双金属离子/单金属离子核糖核酸酶切割反应机制：全水合模型体系的第一性原理分子动力学模拟。

Double-Metal-Ion/Single-Metal-Ion Mechanisms of the Cleavage Reaction of Ribozymes: First-Principles Molecular Dynamics Simulations of a Fully Hydrated Model System.

机构信息

Institute of Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan, Division of Frontier Research, Creative Research Initiative "Sousei", Hokkaido University, Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021, Japan, and Research Institute for Computational Sciences, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.

出版信息

J Chem Theory Comput. 2005 Sep;1(5):925-34. doi: 10.1021/ct050066q.

DOI:10.1021/ct050066q

PMID: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.

摘要

通过 Car-Parrinello 计算研究了金属阳离子（Mg(2+)）在完全水合的 RNA 酶裂解反应中的作用。我们发现，两种金属催化剂的作用是促进质子从 O(2)(')-H 中提取的最有效方法，这触发了亲核攻击，同时削弱并随后裂解了 P-O(5)(')键。结果表明，去除两个金属阳离子之一会导致活化能增加。此外，我们还发现，在 O(2)(')附近包含在 Mg(2+)配位壳中的一个 OH(-)促进了初始质子提取，并防止其在单金属离子和双金属离子途径中转移到核酶中，这与实验结果一致。这表明，在实际的核酶系统中，在存在 OH(-)阴离子的情况下，双金属离子反应机制相对于单金属离子机制更为有利。