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）：该项目的目标是通过第一个包含所有相关现象（即质子传输、电子传输和质子化）的动态模拟框架来阐明细胞色素 c 氧化酶（CcO）的质子泵送机制可电离的氨基酸。这些现象以耦合方式起作用。因此，质子泵浦机制的完整表征将需要一种统一的方法来对待它们。这将通过 MS-EVB2 模型来完成，该模型是少数能够模拟质子动力学的理论之一，并扩展到包含电子转移和残留物电离。 CcO 不仅是生物能学领域的一个基本问题，而且在医学上也很重要，因为它与癌症、神经退行性疾病和衰老等疾病有关。了解其在正常和高能生理条件下的质子泵送机制将有助于我们了解和对抗这些疾病。此外，开发该框架将为研究电荷转移或质子化依赖性活动非常重要的任何生物系统提供工具。因此，这种方法的使用可能相当广泛。