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Natural engineering of multi-electron biological oxidation & reduction

Natural engineering of multi-electron biological oxidation & reduction
多电子生物氧化自然工程
批准号:
7531812
负责人:
PETER LESLIE DUTTON
金额:
$35.93万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-02-01 至 2010-11-30

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中文摘要
翻译
细胞活动的能量基础及其调节依赖于一系列氧化还原酶蛋白, 生物氧化还原代谢和呼吸膜能量转换。的 底物氧化还原和能量转换的许多催化位点的机制,特别是在 线粒体!呼吸,已经证明由于自然的复杂性而难以通过实验获得, 脆弱人们对它们的了解仍然很少。我们的建议旨在揭示氧化还原的自然工程- 在多电子辅因子和底物的这些位点上进行的耦合质子交换和转移 氧化还原反应我们的方法建立在我们对蛋白质电子隧穿的工程指导方针上, 在上一个赠款期得到加强,以告知简单而强大的阿尔法的重新设计和组装, 螺旋蛋白旨在作为蛋白质为基础的模型,maquettes,多电子催化。 模型将被设计为提供最简单的水溶性或跨膜结构, 捕获天然氧化还原中心的功能特性。它们的简单性和适应性使我们能够 研究呼吸链中尚未解决的催化功能问题。模型将是 在溶液中和电极上用光和电测量方法激活,以逐步解剖 电子转移和质子交换的热力学和动力学。模型将包含所有关键 二电子,多质子辅因子/底物醌,烟酰胺和黄素,以及二和四- 电子衬底O2。我们的定位是专注于可逆能量转换催化的问题, 细胞色素bd的Qo位点中的氢醌-醌,旨在确定 医学上有害的短路和自由基的产生。我们将扩大我们的模型创造一个稳定的氧气 亚铁血红素状态,检查两个和四个电子O2还原和生理上重要的两个- NO和H2 O2的电子化学。有了稳定和适应性强的模型,我们可以利用生理 化学在纳米器件的发展。 人类通过呼吸氧气分解食物,产生健康生活所需的所有能量 并且是细胞调节的核心部分。氧自由基有稳定的缓慢释放是正常的 随着时间的推移会导致细胞损伤、衰老和疾病。在压力下,在许多手术期间, 自由基的爆发可以加速这些有害的过程。这项研究经费 描述了一种新的方法来理解健康的氧化能量供应和控制的基础过程, 以及有害的自由基生成。随着进展,我们将更好地预测和跟踪疾病的发生 并采取行动来减缓或逆转它。
英文摘要
The energetic foundation of cellular activity and its regulation relies on a string of oxidoreductase proteins in biological oxidative and reductive metabolism and respiratory membrane energy conversion. The mechanisms of many catalytic sites of substrate oxidation-reduction and energy conversion, particularly in mitochondria! respiration, have proven to be difficult to access experimentally due to natural complexity and fragility. They remain poorly understood. Our proposal aims to reveal the natural engineering of the redox- coupled proton exchange and transfer operating at these sites of multi-electron cofactor and substrate oxidation-reduction. Our approach builds on our engineering guidelines for protein electron tunneling, strengthened in the last grant period, to inform the de novo design and assembly of simple and robust alpha- helical proteins intended to serve as protein-based models, maquettes, for multi-electron catalysis. Maquettes will be designed to provide the simplest water-soluble or trans-membrane structures that can capture the functional properties of natural redox centers. Their simplicity and adaptability allow us to investigate catalytic functional problems that remain unsolved in the respiratory chain. Maquettes will be activated with light and electrometric methods in solution and on electrodes to dissect step-by-step the thermodynamics and kinetics of electron transfer and proton exchange. Maquettes will incorporate all key two-electron, multi-proton cofactors/substrates quinone, nicotinamide and flavin, and the two-and four- electron substrate O2. We are positioned to focus on the problem of reversible energy conversion catalysis of hydroquinone-quinone in the Qo site of the cytochrome bd aiming to determine the mechanistic root of medically harmful short-circuits and radical generation. We will extend our maquette creation of a stable O2 ferrous heme state, to examine two- and four-electron O2 reduction and the physiologically important two- electron chemistries of NO and H2O2. With stable and adaptable maquettes, we can exploit physiological chemistry in the development of nanoscale devices. The breakdown of food by oxygen respiration in humans produces all the energy needed for a healthy life and is a central part of cellular regulation. It is normal that there is a steady slow release of oxygen radicals that over time cause cellular damage, aging and disease. Under stress, and in during many surgical procedures bursts of radicals can accelerate these deleterious processes. The research of this grant describes a new way to understand the processes underlying healthy oxidative energy supply and control as well as deleterious radical generation. With progress we will be better predict and track the onset of disease and act to slow it or reverse it.
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PROTEIN CONFORMATIONAL CHANGE TRIGGERED BY NI-BCHL-A EXCITATION
  • 批准号:
    7373141
  • 项目类别:
  • 资助金额:
    $0.07万
  • 财政年份:
    2006
  • 负责人:
    PETER LESLIE DUTTON
  • 依托单位:
PROTEIN CONFORMATIONAL CHANGE TRIGGERED BY NI-BCHL-A EXCITATION
  • 批准号:
    7183287
  • 项目类别:
  • 资助金额:
    $0.67万
  • 财政年份:
    2005
  • 负责人:
    PETER LESLIE DUTTON
  • 依托单位:
PROTEIN CONFORMATIONAL CHANGE TRIGGERED BY NI-BCHL-A EXCITATION
  • 批准号:
    6976513
  • 项目类别:
  • 资助金额:
    $0.65万
  • 财政年份:
    2004
  • 负责人:
    PETER LESLIE DUTTON
  • 依托单位:
The Natural Engineering of Internal Electric Fields in Redox Proteins at Differen
  • 批准号:
    6706156
  • 项目类别:
  • 资助金额:
    $12.43万
  • 财政年份:
    2003
  • 负责人:
    PETER LESLIE DUTTON
  • 依托单位:
海外基金