STRUCTURE REFINEMENT & WATER PLACEMENT IN BACTERIORHODOPSIN

结构细化

• 批准号: 6469376
• 负责人: JEROME BAUDRY
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6469376
• 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氧化酶是一种由氧化还原驱动的质子泵，伴侣 将氧气还原为质子的易位 穿过整个膜。 最近解决的X射线结构 细胞色素C氧化酶允许对分子动力学模拟 基础运输过程*。 最终建立质子 泵机制我们研究了底物的运输，氧气 和质子，通过酶（请参阅参考文献[75]）。 分子 通过蛋白质扩散的动力学模拟显示 从疏水腔开始的氧结合位点的途径 附近的子单位I的膜暴露表面靠近 sub-Unit III的接口。 大量的水站点是 预测蛋白质。 我们发现水分子形成 质子可以从细胞质进入的两个通道 （矩阵）蛋白质的一侧并到达双核中心。 这些 研究表明，将氧引导到催化中心 沿着明确的路径的酶。 疏水腔 路径的开头可以用作氧气和水的水库 分子可能对质子转移至关重要 细胞色素C氧化酶。 涉及一个可能的抽水机制 谷氨酸侧链的穿梭运动，然后可以 已经提出了将质子转移到血红素A3的丙酸酯组中。