通过DNA/RNA聚合酶催化核酸聚合的自我激活机制
Vito Genna1,2, Pietro Vidossich2, Emiliano Ippoliti2
1Laboratory of Molecular Modeling & Drug Discovery, Istituto Italiano di Tecnologia , Via Morego 30, 16163, Genoa, Italy.
Journal of the American Chemical Society
|August 18, 2016
概括
DNA/RNA聚合酶使用一种新的自我激活机制 (SAM) 进行遗传. 这种机制涉及一个关键的H键,使得有效的核酸添加和DNA/RNA转位,与之前的假设不同.
科学领域:
- 生物化学
- 分子生物学
- 遗传学
背景情况:
- 通过DNA/RNA聚合酶 (Pol) 的DNA和RNA的酶聚合是基因遗传的基础.
- 现有的Pol催化模型不能完全解释基质结合,核酸添加和转移的效率和协调.
研究的目的:
- 阐明以前未知的H键相互作用在聚合酶的迈凯利斯复合体中.
- 提出并验证一种用于聚合酶催化的新型自我激活机制 (SAM).
主要方法:
- 生物信息学分析以确定保存的相互作用.
- 在人类DNA聚合酶上的量子力学/分子力学 (QM/MM) 模拟.
主要成果:
- 在迈凯利斯复合体中发现了输入核酸的3'-OH和β-酸盐部分之间的保存H键.
- 已识别的H键支持一种新型的自我激活机制 (SAM),该机制整合了核友的形成,核酸的添加和转移.
- QM/MM模拟证实了人类DNA聚合酶-η的建议SAM.
结论:
- 新的自我激活机制 (SAM) 为聚合酶催化提供了一个优雅而高效的模型,与之前的假设不同.
- 跨DNA和RNA聚合酶的结构保护表明SAM可能是生命的三个领域的通用机制.
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