Simulating the fidelity and the three Mg mechanism of pol η and clarifying the validity of transition state theory in enzyme catalysis.
Simulating the fidelity and the three Mg mechanism of pol η and clarifying the validity of transition state theory in enzyme catalysis.
复制标题
模拟pol δ的保真度和三镁机理，阐明过渡态理论在酶催化中的有效性。
DOI：
10.1002/prot.25305
复制
发表时间：
2017
期刊：
影响因子：
2.9
通讯作者：
Warshel,Arieh
中科院分区：
文献类型：
--
作者：
Yoon,Hanwool;Warshel,Arieh
Pol η属于DNA聚合酶的重要Y家族，其可以催化跨损伤DNA位点的跨损伤合成。该活性涉及Pol η对8-oxo-7，8-diedro-2′-deoxoguanosin（8-oxoG）的保真度降低。随着第三个Mg ~（2+）离子的重要性的证明，对Pol η的基本兴趣最近有所增长。目前的工作探索的保真度Pol η和第三金属离子的作用，通过使用经验价键（EVB）模拟。模拟再现了观察到的保真度趋势，并揭示了第三金属离子的作用。据发现，这种离子不会导致一个主要的催化作用，但最有可能发挥重要作用，降低产品的释放障碍。此外，它的结论是，在对比的一些影响，这种金属的效果并不违反过渡态理论，和催化效果的评价必须保存从反应物移动到过渡态时的分子组成。蛋白质2017; 85：1446-1453。© 2017 Wiley Periodicals，Inc.
Pol η belongs to the important Y family of DNA polymerases that can catalyze translesion synthesis across sites of damaged DNA. This activity involves the reduced fidelity of Pol η for 8‐oxo‐7,8‐dhyedro‐2′‐deoxoguanosin(8‐oxoG). The fundamental interest in Pol η has grown recently with the demonstration of the importance of a 3rd Mg2+ ion. The current work explores both the fidelity of Pol η and the role of the 3rd metal ion, by using empirical valence bond (EVB) simulations. The simulations reproduce the observed trend in fidelity and shed a new light on the role of the 3rd metal ion. It is found that this ion does not lead to a major catalytic effect, but most probably plays an important role in reducing the product release barrier. Furthermore, it is concluded, in contrast to some implications, that the effect of this metal does not violate transition state theory, and the evaluation of the catalytic effect must conserve the molecular composition upon moving from the reactant to the transition state. Proteins 2017; 85:1446–1453. © 2017 Wiley Periodicals, Inc.