Mechanistic studies of a bifurcating flavoprotein

分叉黄素蛋白的机理研究

• 批准号: 10410411
• 负责人: Russ Hille
• 金额: $ 29.62万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410411
• 关键词: Biological; Carbon Dioxide; Cells; Coenzyme A; Complex; Coupled; Cryoelectron Microscopy; Defect; Dependence; Disease; Electron Transport; Electron transfer flavoprotein; Electrons; Ensure; Enzymes; Event; Family; Ferredoxin; Ferredoxin-NAD+ reductase; Flavodoxin; Flavoproteins; Functional disorder; Goals; Human; Individual; Iron-Sulfur Proteins; Isotopes; Kinetics; Metabolism; Mitochondria; Molecular; Monitor; Motion; Multienzyme Complexes; NADH; NADP; Oxidants; Oxidation-Reduction; Pathway interactions; Physiological; Play; Process; Pyrobaculum; Pyruvate; Quinones; Reaction; Role; Solvents; Spectrophotometry; Structure; System; Thermodynamics; Ubiquinone; Vitamin K 2; Work; base; deprotonation; electron donor; electron-transferring-flavoprotein dehydrogenase; enzyme model; experimental study; fatty acid oxidation; human disease; member; microorganism; protonation; sample fixation

Project Summary Electron-transferring flavoproteins (ETFs) are a large and broadly distributed family of electron carriers that play critical roles in a variety of metabolic processes, including b-oxidation of fatty acids in humans. Defects in ETFs give rise to several specific disease states. A subset of the ETF family constitute a recently discovered class of complex flavoproteins that catalyze the coupled reduction of high- and low-potential electron acceptors using a median-potential electron donor in a process referred to as electron bifurcation. An example of such a bifurcating ETF is the EtfABCX system from Pyrobaculum aerophilum. This enzyme accepts reducing equivalents from NADH, passing the reducing equivalents on to the high-potential menaquinone and the low-potential iron- sulfur protein ferredoxin in a manner that is overall thermodynamically favorable. The proposed work will examine in detail the kinetics of electron bifurcation as catalyzed by EtfABCX, critically evaluating the involvement of protonation/deprotonation processes associated with the primary electron transfer events.

项目总结