Molecular mechanism of redox driven proton pumps

氧化还原驱动质子泵的分子机制

• 批准号: 7895528
• 负责人: MARIAN FABIAN
• 金额: $ 22.88万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895528
• 关键词: ATP Hydrolysis; Address; Aging; Apoptosis; Attention; Bacteriorhodopsins; Binding; Binding Proteins; Biochemical; Bioenergetics; Catalytic Domain; Cattle; Complex; Coupled; Coupling; Cytochrome bc1 Complex; Defect; Degenerative Disorder; Detergents; Dioxygen; Electron Spin Resonance Spectroscopy; Electron Transport; Electrons; Enzymes; Free Energy; Free Radicals; Freezing; Functional disorder; Generations; Goals; Heart; Heme; Heme aa3 Cytochrome Oxidase; Hydrogen; Investigation; Kinetics; Ligand Binding; Light; Link; Malignant Neoplasms; Medical; Membrane; Membrane Transport Proteins; Methods; Mitochondria; Mitochondrial Diseases; Modeling; Molecular; Molecular Machines; Movement; Nature; Nitric Oxide; Optics; Oxidases; Oxidation-Reduction; Oxygen; Phospholipids; Photosynthetic Reaction Centers; Principal Investigator; Process; Proteins; Proton Pump; Protons; Pump; Reaction; Research; Respiration; Rhodobacter sphaeroides; Side; Signaling Molecule; Site; Source; Structure; Submitochondrial Particles; Testing; Thermodynamics; Time; Transducers; Variant; Vesicle; Water; biological systems; chemical reaction; copper oxidase; cytochrome c oxidase; design; flash photolysis; interest; oxidation; prevent; programs; research study; respiratory

Coupled electron and proton transfer is recognized as the universal principle of primary energy conservation in respiration. Terminal respiratory oxidases are membrane-bound electron- transfer complexes that catalyze the reduction of oxygen to water and this reaction is associated with the generation of a transmembrane proton gradient that is the primary source of cellular free energy. Oxidases utilize two basic principles to produce the proton gradient. The first is a classical Mitchell's loop mechanism in which electrons and protons for the water formation are taken up from the opposite sides of membrane. The second one is proton pumping in which proton transfer across the membrane is driven by the free energy provided by a redox reaction. However, the mechanism of proton pumping has not been elucidated in any proton pump driven by reduction-oxidation reactions and it remains one of the key problems of molecular bioenergetics. Proposed investigations will contribute to an understanding of the proton translocation mechanism by identification of the electron-proton coupling sites and experimental examination and establishment of the mechanistic principles of pumping and proton gating in heme-copper oxidases. The application of optical spectroscopy, electron paramagnetic resonance, rapid freeze-quenching, flash photolysis, stopped-flow, and several biochemical methods will be utilized to achieve these goals. Specific aims will be addressed using the purified bovine heart oxidase, enzyme incorporated into phospholipid vesicles and in submitochondrial particles.

电子和质子的耦合转移被认为是一次能量的普遍原理