Proton-pumping mechanism of cytochrome c oxidase: a kinetic master-equation approach.
Proton-pumping mechanism of cytochrome c oxidase: a kinetic master-equation approach.
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细胞色素c氧化酶的质子泵浦机制：动力学主方程方法。
DOI：
10.1016/j.bbabio.2011.09.004
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hummer,Gerhard
中科院分区：
文献类型：
--
作者：
Kim,YoungC;Hummer,Gerhard
细胞色素c氧化酶是一种有效的能量转换器，它将氧还原为水，并将释放的化学能转化为电化学膜电位。作为一个真正的质子泵，细胞色素c氧化酶将质子转移到膜上。基于大量的实验和计算，氧化还原循环中反应中间体的详细情况越来越多。然而，质子泵送与氧化还原化学耦合的基本机制在很大程度上仍未得到解决。在这里，我们研究并扩展了动力学主方程方法，以深入了解细胞色素c氧化酶中氧化还原偶联的质子泵送。细胞色素c氧化酶质子泵的基本原理来自于对最简单的动力学模型的分析，这些模型保留了实验确定的结构、能量学和动力学的基本要素，并满足基本的物理原理。主方程模型使我们能够解决在一个所有反应步骤都可逆的系统中如何实现抽运的问题。而质子抽运不需要直接调制微观反应势垒，这种动力学门控大大提高了抽运效率。进一步的效率提高可以通过质子摄取途径从活性位点区域部分解耦来实现。这种机制与提出的Glu阀一致，其中关键谷氨酸的侧链在D通道和活性位点区域之间穿梭。我们还表明，即使在没有周转的情况下，模型也只能预测小的质子泄漏。这里确定的细胞色素c氧化酶的设计原则为新型生物启发的燃料电池提供了蓝图，并且主方程公式也应该证明对其他分子机器有用。这篇文章是题为“呼吸氧化酶”的特刊的一部分。
Cytochrome c oxidase is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, cytochrome c oxidase translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in cytochrome c oxidase. Basic principles of the cytochrome c oxidase proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the active-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for cytochrome c oxidase provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. This article is part of a Special Issue entitled: Respiratory Oxidases.