Sharma Vivek, Enkavi Giray, Vattulainen Ilpo, Róg Tomasz, Wikström Mårten
Department of Physics, Tampere University of Technology, FI-33101, Tampere, Finland;
Department of Physics, Tampere University of Technology, FI-33101, Tampere, Finland; MEMPHYS - Center for Biomembrane Physics, Department of Physics, University of Southern Denmark, DK-5230, Odense, Denmark; and.
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2040-5. doi: 10.1073/pnas.1409543112. Epub 2015 Feb 2.
Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O-O bond splitting transition of the catalytic cycle (A → P(R)), it has been proposed that the electron transfer to the binuclear iron-copper center of O2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane-solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redox-state-dependent organization of water molecules within the protein structure that gates the proton transfer pathway.
分子氧作为需氧生物呼吸链中的终端电子受体。线粒体内膜和细菌质膜中的细胞色素c氧化酶催化氧气还原为水，并将反应的自由能与质子跨膜泵出相偶联。质子泵出活性有助于形成质子电化学梯度，从而驱动ATP的合成。基于对催化循环中O - O键断裂转变（A→P(R)）的动力学实验，有人提出电子转移至O₂还原的双核铁 - 铜中心启动了质子泵机制。这一关键的电子转移事件与一个内部质子转移相偶联，该质子从一个保守的谷氨酸转移至泵的质子加载位点。然而，质子也可能转而转移至双核中心以完成氧还原化学过程，这将构成一个短路。基于在明确的膜 -溶剂环境中对细胞色素c氧化酶进行的原子分子动力学模拟，并辅以相关的自由能计算，我们提出通过蛋白质结构内水分子的氧化还原状态依赖性组织来有效防止这种短路，该组织控制着质子转移途径。
