Peng Yuxing, Voth Gregory A
Department of Chemistry, University of Chicago, Chicago, IL, USA.
Biochim Biophys Acta. 2012 Apr;1817(4):518-25. doi: 10.1016/j.bbabio.2011.11.017. Epub 2011 Dec 8.
In cytochrome c oxidase (CcO), a redox-driven proton pump, protons are transported by the Grotthuss shuttling via hydrogen-bonded water molecules and protonatable residues. Proton transport through the D-pathway is a complicated process that is highly sensitive to alterations in the amino acids or the solvation structure in the channel, both of which can inhibit proton pumping and enzymatic activity. Simulations of proton transport in the hydrophobic cavity showed a clear redox state dependence. To study the mechanism of proton pumping in CcO, multi-state empirical valence bond (MS-EVB) simulations have been conducted, focusing on the proton transport through the D-pathway and the hydrophobic cavity next to the binuclear center. The hydration structures, transport pathways, effects of residues, and free energy surfaces of proton transport were revealed in these MS-EVB simulations. The mechanistic insight gained from them is herein reviewed and placed in context for future studies.
在细胞色素c氧化酶（CcO）中，一种由氧化还原驱动的质子泵，质子通过Grotthuss穿梭机制，经由氢键连接的水分子和可质子化残基进行传输。质子通过D途径的传输是一个复杂的过程，对通道中氨基酸的改变或溶剂化结构高度敏感，这两者都会抑制质子泵浦和酶活性。在疏水腔中质子传输的模拟显示出明显的氧化还原状态依赖性。为了研究CcO中质子泵浦的机制，已经进行了多态经验价键（MS-EVB）模拟，重点关注质子通过D途径和双核中心旁边的疏水腔的传输。这些MS-EVB模拟揭示了质子传输的水合结构、传输途径、残基的影响以及自由能表面。本文对从中获得的机理见解进行了综述，并为未来的研究提供了背景。
