Mechanistic studies of a bifurcating flavoprotein

分叉黄素蛋白的机理研究

• 批准号: 10201670
• 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/10201670
• 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.

项目概要 电子转移黄素蛋白 (ETF) 是一个庞大且分布广泛的家族 电子载体在各种代谢过程中发挥关键作用，包括 b-氧化 人体中的脂肪酸。 ETF 的缺陷会导致几种特定的疾病状态。的一个子集 ETF 家族构成了最近发现的一类复杂黄素蛋白，可催化偶联 使用中电位电子供体还原高电位和低电位电子受体 过程称为电子分岔。这种分叉 ETF 的一个例子是 EtfABCX 来自 Pyrobaculum aerophilum 的系统。该酶接受 NADH 的还原当量， 将还原当量传递给高电位甲基萘醌和低电位铁- 硫蛋白铁氧还蛋白以总体热力学有利的方式。拟议的 这项工作将详细研究 EtfABCX 催化的电子分岔动力学，批判性地 评估与初级相关的质子化/去质子化过程的参与 电子转移事件。