Park Hwangseo, Lee Sangyoub
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Korea, and Department of Chemistry, Seoul National University, Seoul 151-747, Korea.
J Chem Theory Comput. 2006 May;2(3):858-62. doi: 10.1021/ct0503015.
Structural and mechanistic studies of the hairpin ribozyme have been actively pursued over the last two decades to understand its catalytic strategy for RNA hydrolysis. Based on molecular dynamics simulations with the newly developed force field parameters for a vanadium-oxygen complex, we investigate the dynamic properties of the hairpin ribozyme in complex with a transition state analogue for the phosphodiester cleavage. The results indicate that the three nucleobases of the hairpin ribozyme (G8, A9, and A38) stabilize the negatively charged oxygen atoms in the transition state through the formation of five hydrogen bonds, which is consistent with the X-ray crystallographic data. In addition to the three catalytic nucleobases, several solvent molecules are also found to contribute to the catalytic action of the hairpin ribozyme by hydrogen bond stabilization of the negatively charged oxygens as well as by optimally positioning the catalytic nucleobases in the active site.
在过去二十年中，人们一直积极开展对发夹状核酶的结构和机制研究，以了解其RNA水解的催化策略。基于使用新开发的钒 - 氧络合物力场参数进行的分子动力学模拟，我们研究了与磷酸二酯裂解过渡态类似物结合的发夹状核酶的动力学性质。结果表明，发夹状核酶的三个核碱基（G8、A9和A38）通过形成五个氢键来稳定过渡态中带负电荷的氧原子，这与X射线晶体学数据一致。除了这三个催化核碱基外，还发现几个溶剂分子通过对带负电荷的氧进行氢键稳定以及将催化核碱基在活性位点中优化定位，对发夹状核酶的催化作用有贡献。
