NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, Illinois 61801, United States.
Department of Physics, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, Illinois 61801, United States.
J Am Chem Soc. 2021 Jan 20;143(2):715-723. doi: 10.1021/jacs.0c07799. Epub 2021 Jan 5.
The cytochrome complex is a transmembrane enzymatic protein complex that plays a central role in cellular energy production and is present in both photosynthetic and respiratory chain organelles. Its reaction mechanism is initiated by the binding of a quinol molecule to an active site, followed by a series of charge transfer reactions between the quinol and protein subunits. Previous work hypothesized that the primary reaction was a concerted proton-coupled electron transfer (PCET) reaction because of the apparent absence of intermediate states associated with single proton or electron transfer reactions. In the present study, the kinetics of the primary complex PCET reaction is investigated with a vibronically nonadiabatic PCET theory in conjunction with all-atom molecular dynamics simulations and electronic structure calculations. The computed rate constants and relatively high kinetic isotope effects are consistent with experimental measurements on related biomimetic systems. The analysis implicates a concerted PCET mechanism with significant hydrogen tunneling and nonadiabatic effects in the complex. Moreover, the employed theoretical framework is shown to serve as a general strategy for describing PCET reactions in bioenergetic systems.
细胞色素 c 氧化还原酶复合物是一种跨膜酶蛋白复合物，在细胞能量产生中起着核心作用，存在于光合和呼吸链细胞器中。其反应机制由醌分子与活性位点的结合引发，随后在醌和蛋白亚基之间发生一系列电荷转移反应。先前的工作假设主要反应是协同质子耦合电子转移（PCET）反应，因为与单个质子或电子转移反应相关的中间态明显不存在。在本研究中，使用带有非绝热 PCET 理论的振动力学与全原子分子动力学模拟和电子结构计算相结合，研究了初级细胞色素 c 氧化还原酶复合物 PCET 反应的动力学。计算得到的速率常数和相对较高的动力学同位素效应与相关仿生系统的实验测量结果一致。分析表明，在细胞色素 c 氧化还原酶复合物中存在协同 PCET 机制，其中涉及显著的氢隧穿和非绝热效应。此外，所采用的理论框架被证明是描述生物能系统中 PCET 反应的一般策略。
