Mechanistic studies of a bifurcating flavoprotein

分叉黄素蛋白的机理研究

• 批准号: 10387414
• 负责人: Russ Hille
• 金额: $ 13.19万
• 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/10387414
• 关键词: Complex; Coupled; Cryoelectron Microscopy; Defect; Disease; Electron Transport; Electron transfer flavoprotein; Electrons; Enzymes; Event; Family; Ferredoxin; Ferredoxin-NAD+ reductase; Flavins; Flavoproteins; Functional disorder; Goals; Human; Iron; Iron-Sulfur Proteins; Kinetics; Metabolism; Mitochondria; Molecular; Motion; NADH; Oxidants; Play; Process; Pyrobaculum; Quinones; Reaction; Role; Signal Transduction; Structure; Sulfur; System; Thermodynamics; Vitamin K 2; Work; base; deprotonation; electron donor; enzyme model; fatty acid oxidation; human disease; member; protonation; semiquinone

Project Abstract 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 -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.

项目摘要 电子转移黄素蛋白（ETFs）是一个大的和广泛分布的家族， 电子载体，在各种代谢过程中发挥关键作用，包括β-氧化 人体内的脂肪酸ETF的缺陷会导致几种特定的疾病状态。的子集 ETF家族构成了最近发现的一类复杂的黄素蛋白，其催化偶联的 使用中位电子供体还原高电位和低电位电子受体， 这个过程称为电子分叉。这种分叉ETF的一个例子是EtfABCX Pyrobaculum aerophilum.这种酶接受来自NADH的还原当量， 将还原当量传递到高电位甲萘醌和低电位铁上- 硫蛋白铁氧还蛋白以总体上有利的方式。拟议 工作将详细研究EtfABCX催化的电子分叉动力学， 评估与初级质子化/去质子化过程相关的参与 电子转移事件