Proton Pumping in Cytochrome c Oxidase

细胞色素 c 氧化酶中的质子泵送

• 批准号: 7286253
• 负责人: Jessica Swanson
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7286253
• 关键词: ATP Synthesis Pathway; Accounting; Active Sites; Address; Aging; Amino Acids; Bioenergetics; Biological; Biomedical Research; Charge; Condition; Coupled; Couples; Curiosities; Development; Disease; Electron Transport; Electron-Transport Chain of the Respiratory Enzymes; Electrons; Enzymes; Equilibrium; Fellowship; Free Energy; Future; Goals; Individual; Investigation; Knowledge; Link; Malignant Neoplasms; Membrane; Methodology; Methods; Modeling; Movement; Names; Nerve Degeneration; Numbers; Object Attachment; Oxidation-Reduction; Pathway interactions; Physiological; Production; Property; Proteins; Proton Pump; Protons; Pump; Scheme; Series; Side; Simulate; Surface; System; Theoretical model; Water; Work; career; cytochrome c oxidase; experience; fight against; ionization; protonation; quantum; research study; simulation; theories; tool; uptake

DESCRIPTION (provided by applicant): The goal of this project is to elucidate the proton pumping mechanism of cytochrome c oxidase (CcO) with the first dynamical simulation framework to incorporate all of the relevant phenomena, namely proton transport, electron transport, and the protonation of ionizable amino acids. These phenomena act in a coupled manner. Thus, the complete characterization of the proton pumping mechanism will require a unified methodology that treats them as such. This will be accomplished with the MS-EVB2 model, one of a few theories able to simulate proton dynamics, extended to incorporate electron transfer and residue ionization. CcO is not only a fundamental curiosity within bioenergetics, it is also medically important having been linked to diseases such as cancer, neurodegeneration, and aging. Understanding its proton pumping mechanism under normal and high energy physiological conditions will contribute to our knowledge of and fight against these diseases. Additionally, developing this framework will provide a tool for investigating any biological system where charge transfer or protonation-dependent activity is of importance. Thus, the use of this methodology is potentially quite broad.

描述（由申请人提供）：该项目的目的是阐明具有第一个动力学模拟框架的细胞色素C氧化酶（CCO）的质子泵送机理，以结合所有相关现象，即质子传输，电子传输，电子传输和质子氨基酸的质子化。这些现象以耦合方式起作用。因此，质子泵送机制的完整表征将需要一种将其视为这样的统一方法。这将通过MS-EVB2模型（一种能够模拟质子动力学的少数理论之一）来完成，该模型扩展了以结合电子传递和残基电离。 CCO不仅是生物能力学中的基本好奇心，而且与癌症，神经退行性变化和衰老等疾病有关，它在医学上也是重要的。了解其在正常和高能量生理条件下的质子抽水机制将有助于我们对这些疾病的了解并抗击。此外，开发此框架将提供一种工具，用于研究任何生物系统，而在电荷转移或质子化依赖性活动至关重要的情况下。因此，这种方法的使用可能很广泛。