STRUCTURE REFINEMENT & WATER PLACEMENT IN BACTERIORHODOPSIN

结构细化

• 批准号: 6348219
• 负责人: JEROME BAUDRY
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348219
• 关键词: aging; biological products; biomedical resource; enzymes; model design /development; respiratory system; structural biology; technology /technique

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.

细胞色素 c 氧化酶是一种氧化还原驱动的质子泵，它耦合 氧还原成水到质子的易位 穿过膜。 最近解决的X射线结构 细胞色素c氧化酶允许分子动力学模拟 底层传输过程*。 最终建立质子 泵机制我们研究了底物、氧气的传输 和质子，通过酶（参见参考文献[75]）。 分子 氧通过蛋白质扩散的动力学模拟揭示 从疏水腔开始到达氧结合位点的途径 靠近子单元I的膜暴露表面，靠近 与子单元 III 的接口。 大量水域被 预测在蛋白质内。 我们发现水分子形成 质子可以从细胞质进入的两个通道 蛋白质的（基质）侧并到达双核中心。 这些 研究表明氧气被引导至催化中心 the enzyme along a well defined path. 疏水性空腔 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包括 谷氨酸侧链的穿梭运动，然后可以 有人提议将质子转移到血红素 a3 的丙酸基团上。