Hofacker I, Schulten K
Beckman Institute, University of Illinois at Urbana-Champaign 61801, USA.
Proteins. 1998 Jan;30(1):100-7.
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 investigate the transport of the substrates, oxygen and protons, through the enzyme. Molecular dynamics simulations of oxygen diffusion through the protein reveal a well-defined pathway to the oxygen-binding site starting at a hydrophobic cavity near the membrane-exposed surface of subunit I, close to the interface to subunit III. A large number of water sites are predicted within the protein, which could play an essential role for the transfer of protons in cytochrome c oxidase. The water molecules form two channels along which protons can enter from the cytoplasmic (matrix) side of the protein and reach the binuclear center. A possible pumping mechanism is proposed that involves a shuttling motion of a glutamic acid side chain, which could then transfer a proton to a propionate group of heme alpha 3.
细胞色素c氧化酶是一种由氧化还原驱动的质子泵，它将氧气还原为水的过程与质子跨膜转运相偶联。最近解析出的细胞色素c氧化酶的X射线结构使得对其潜在转运过程进行分子动力学模拟成为可能。为最终确立质子泵机制，我们研究了底物（氧气和质子）通过该酶的转运情况。对氧气在蛋白质中扩散的分子动力学模拟揭示了一条从亚基I膜暴露表面附近的疏水腔开始、通向氧气结合位点的明确路径，该疏水腔靠近与亚基III的界面。预计蛋白质内部存在大量的水位点，这些水位点可能在细胞色素c氧化酶的质子转移过程中发挥关键作用。水分子形成两条通道，质子可沿着这两条通道从蛋白质的胞质（基质）侧进入并到达双核中心。提出了一种可能的泵浦机制，该机制涉及谷氨酸侧链的穿梭运动，然后谷氨酸侧链可将一个质子转移至血红素α3的丙酸基团。
