STRUCTURE REFINEMENT & WATER PLACEMENT IN BACTERIORHODOPSIN

细胞色素c氧化酶是一种氧化还原驱动的质子泵，它与 氧到水的还原为质子的转移 穿过薄膜。新近解决的X射线结构 细胞色素C氧化酶允许分子动力学模拟 基础运输流程*。最终建立起质子 泵浦机制我们研究了底物氧气的传输 和质子，通过酶(见参考文献[75])。分子 氧通过蛋白质扩散的动力学模拟揭示 从疏水空腔开始通向氧结合部位的路径 靠近第I分机组的膜裸露表面，靠近 与第三分单元的接口。大量的水址 在蛋白质中预测的。我们发现水分子形成了 质子可以从细胞质进入的两个通道 (基质)蛋白的一侧，并到达双核中心。这些 研究表明，氧被引导到催化中心 这种酶沿着一条明确的路径。的疏水空腔 这条小路的起点可以作为氧气和水的蓄水池 分子可能在质子转移中起重要作用。 细胞色素c氧化酶。一种可能的抽气机制，涉及一种 谷氨酸侧链的穿梭运动，然后它可以 已经提出了将质子转移到血红素A3的丙酸基上。

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.