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Mechanistic studies of a bifurcating flavoprotein

分叉黄素蛋白的机理研究

基本信息

批准号：
10640091
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
项目类别：
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/10640091
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 Oxidoreductase Pathway interactions Physiological Play Process Pyrobaculum Pyruvate Quinones Reaction Role Solvents Spectrophotometry Structure System Thermodynamics Ubiquinone Vitamin K 2 Work deprotonation electron donor electron-transferring-flavoprotein dehydrogenase enzyme model experimental study fatty acid oxidation human disease member microorganism protonation sample fixation

项目摘要

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

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A new era for electron bifurcation.

DOI：
10.1016/j.cbpa.2018.07.026
发表时间：
2018-12
期刊：
Current opinion in chemical biology
影响因子：
7.8
作者：
通讯作者：

Correlating Conformational Equilibria with Catalysis in the Electron Bifurcating EtfABCX of Thermotoga maritima.

DOI：
10.1021/acs.biochem.3c00472
发表时间：
2024-01-02
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Murray, Daniel T.;Ge, Xiaoxuan;Schut, Gerrit J.;Rosenberg, Daniel J.;Hammel, Michal;Bierma, Jan C.;Hille, Russ;Adams, Michael W. W.;Hura, Greg L.
通讯作者：
Hura, Greg L.

Spectral deconvolution of redox species in the crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase from Megasphaera elsdenii. A flavin-dependent bifurcating enzyme.

DOI：
10.1016/j.abb.2021.108793
发表时间：
2021-04-15
期刊：
Archives of biochemistry and biophysics
影响因子：
3.9
作者：
Vigil W Jr;Niks D;Franz-Badur S;Chowdhury N;Buckel W;Hille R
通讯作者：
Hille R

Characterization of the Membrane-Associated Electron-Bifurcating Flavoenzyme EtfABCX from the Hyperthermophilic Bacterium Thermotoga maritima.

DOI：
10.1021/acs.biochem.3c00473
发表时间：
2023-12-19
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Ge, Xiaoxuan;Schut, Gerrit J.;Tran, Jessica;Poole II, Farris L.;Niks, Dimitri;Menjivar, Kevin;Hille, Russ;Adams, Michael W. W.
通讯作者：
Adams, Michael W. W.

Xanthine Oxidase-A Personal History.