4.5 Article

Modeling the RNA 2′OH Activation: Possible Roles of Metal Ion and Nucleobase as Catalysts in Self-Cleaving Ribozymes

期刊

JOURNAL OF PHYSICAL CHEMISTRY B
卷 115, 期 37, 页码 10943-10956

出版社

AMER CHEMICAL SOC
DOI: 10.1021/jp200970d

关键词

-

资金

  1. Czech Science Foundation [204/09/J010]
  2. Ministry of Education, Youth and Sports of the Czech Republic [ME09062, CZ.I.07/2.3.00/09.0076]
  3. CNRS (ATIP, France)

向作者/读者索取更多资源

The RNA 2'OH activation as taking place in the first chemical step of self-cleaving ribozymes is studied theoretically by DFT and MP2 methods using a continuum solvation model (CPCM). The reaction of proton transfer is studied in the presence of two kinds of catalysts: a fully hydrated metal ion (Mg2+) or partially hydrated nucleobase (guanine), taken separately or together leading to three different modes of activation. The metal ion is either directly bound (inner-sphere) or indirectly bound (outer-sphere) to the 2'OH group and a hydroxide ion acts as a general or specific base; the nucleobase is taken in anionic or in neutral enoltautomeric forms playing itself the role of general base. The presence of a close metal ion (outer-sphere) lowers the pK(a) value of the 2'OH group by several log units in both metal-ion and nuleobase catalysis. The direct metal coordination to the 2'OH group (inner-sphere) further stabilizes the developing negative charge on the nucleophile. The switching from the inner-sphere to the outer-sphere coordination appears to be driven by the energy cost for reorganizing the first coordination shell rather than by the electrostatic repulsion between the ligands. The metal-ion catalysis is more effective with a specific base in the dianionic mechanism. On the other hand, the nucleobase catalysis is more effective in the monoanionic mechanism and in the presence of a metal ion acting as a cofactor through nonspecific electrostatic interactions. The results establish a baseline to study the possible roles of metal and nudeobase catalysts and their environment in more realistic models for self-cleaving ribozymes.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据