OXYGEN & PROTON PATHWAYS IN CYTOCHROME C OXIDASE

细胞色素c氧化酶是一种氧化还原驱动的质子泵，它偶联 氧气还原为水，质子转移 穿过细胞膜 最近解决的x射线结构的 细胞色素c氧化酶允许分子动力学模拟 基本运输过程 *。 最终建立质子 泵浦机制，我们研究了基板，氧气的传输 和质子通过酶（参见参考文献[75]）。 分子 氧气通过蛋白质扩散的动力学模拟显示， 从疏水空腔开始的通向氧结合位点的通路 靠近亚单元I的膜暴露表面，靠近 与次级单元III的接口。 大量的水资源被 在蛋白质中预测。 我们发现水分子的形成 质子可从细胞质进入的两个沿着通道 （基质）侧并到达双核中心。 这些 研究表明，氧气被引导到催化中心， 酶沿着一个明确的路径。 路径的起点可以作为氧气和水的储存库 分子可能在质子转移中发挥重要作用 细胞色素c氧化酶 一种可能的泵送机制， 谷氨酸侧链的穿梭运动， 已经提出了将质子转移到血红素A3的丙酸酯基团。

Cytochrome c oxidase is a redox-driven proton pump, which couples the reduction of oxygen to water to the translocation of protons across the membrane. The recently solved x-ray structures of cytochrome c oxidase permit molecular dynamics simulations of the underlying transport processes*. To eventually establish the proton pump mechanism we investigated the transport of the substrates, oxygen and protons, through the enzyme (see reference [75]). Molecular dynamics simulations of oxygen diffusion through the protein revealed a pathway to the oxygen binding site starting at a hydrophobic cavity near the membrane exposed surface of sub-unit I, close to the interface to sub-unit III. A large number of water sites was predicted within the protein. We found that the water molecules form two channels along which protons can enter from the cytoplasmic (matrix) side of the protein and reach the binuclear center. These studies suggest that oxygen is channeled to the catalytic center of the enzyme along a well defined path. Hydrophobic cavities at the start of the path could serve as reservoirs for oxygen, and water molecules might play an essential role for the transfer of protons in cytochrome c oxidase. A possible pumping mechanism that involves a shuttling motion of a glutamic acid side chain, which could then transfer a proton to a propionate group of heme a3, has been proposed.