Convergence of Theory and Experiment on the Role of Preorganization, Quantum Tunneling, and Enzyme Motions into Flavoenzyme-Catalyzed Hydride Transfer
Convergence of Theory and Experiment on the Role of Preorganization, Quantum Tunneling, and Enzyme Motions into Flavoenzyme-Catalyzed Hydride Transfer
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DOI：
10.1021/acscatal.7b00201
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发表时间：
2017-05-01
期刊：
影响因子：
12.9
通讯作者：
Tunon, Inaki
中科院分区：
文献类型：
--
作者：
Delgado, Manuel;Gorlich, Stefan;Tunon, Inaki
氢化物转移是酶催化体系中最常见的反应之一，由于可能存在显著的量子隧穿效应而成为研究的对象。在本工作中，我们提供了一个结合的理论QM/MM模拟和实验测量的速率常数和动力学同位素效应（KIE）的吗啡酮还原酶催化的氢化物转移反应，MR量子力学隧道系数，计算在变分过渡态理论的框架，在这个反应中发挥了重要作用，对于最轻的同位素体，达到23.8 +/-5.5的值--酶系统报道的最大值之一。理论预测的速率常数和相应的实验值之间的协议支持这一预测。模拟结果表明，蛋白质运动的作用可以令人满意地描述为平衡波动沿着反应坐标，符合高度的预组织显示这种酶。
Hydride transfer is one of the most common reactions catalyzed by enzymatic systems, and it has become an object of study because of possible significant quantum tunneling effects. In the present work, we provide a combination of theoretical QM/MM simulations and experimental measurements of the rate constants and kinetic isotopic effects (KIEs) for the hydride transfer reaction catalyzed by morphinone reductase, MR Quantum mechanical tunneling coefficients, computed in the framework of variational transition-state theory, play a significant role in this reaction, reaching values of 23.8 +/- 5.5 for the lightest isotopologue-one of the largest values reported for enzymatic systems. This prediction is supported by the agreement between the theoretically predicted rate constants and the corresponding experimental values. Simulations indicate that the role of protein motions can be satisfactorily described as equilibrium fluctuations along the reaction coordinate, in line with a high degree of preorganization displayed by this enzyme.