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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。

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

Xanthine Oxidase-A Personal History.

DOI：
10.3390/molecules28041921
发表时间：
2023-02-17
期刊：
MOLECULES
影响因子：
4.6
作者：
Hille, Russ
通讯作者：
Hille, Russ

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.