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(ETF)是一个分布广泛的大家族。 电子载体在各种代谢过程中发挥关键作用，包括-氧化 人类体内的脂肪酸。ETF的缺陷会导致几种特定的疾病状态。属性的子集 ETF家族构成了最近发现的一类复杂的黄素蛋白，它催化偶联 用中电势电子给体减少高电势和低电势电子受体 称为电子分叉的过程。这种分叉ETF的一个例子是EtfABCX 从嗜氧性焦杆菌中分离的菌株。该酶接受来自NADH的还原当量， 将还原当量传递给高电势的孟喹酮和低电势的铁-- 硫蛋白铁氧还蛋白以一种总体热力学上有利的方式。建议数 这项工作将详细研究由EtfABCX催化的电子分叉动力学， 评估与初级粒子相关的质子化/去质子化过程的参与 电子转移事件。