FUNDAMENTALS OF BIOLOGICAL ELECTRON TRANSFER

生物电子转移的基础知识

• 批准号: 6151050
• 负责人: PETER LESLIE DUTTON
• 金额: $ 28.23万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151050
• 关键词: chemical kinetics; cofactor; electron transport; oxidoreductase; peptide chemical synthesis; protein engineering; protein structure function; synthetic peptide

DESCRIPTION: Oxidoreductase dysfunction is becoming recognized as a major contribution to the debilitation of several common diseases that are highly complex with poor prospects for cure. Understanding the principles of function of the different classes of oxidoreductases, and their engineering tolerances and the thresholds of failure would almost certainly help in ameliorating the effects of the illnesses, by providing much needed diagnostic tools and pointing the direction to a cure. This proposal is aimed at understanding a fundamental part of many oxidoreductases, namely the delivery of electrons to and from catalytic or energy coupling sites. The PI plans to apply the consensus and generality extracted from our examination of natural redox protein construction and electron tunneling function to the design, de novo synthesis and assembly of simplified redox proteins; i.e., maquettes. By examing natural redox centers in the relatively simple stable, structurally characterized, heterogeneous peptide environment of maquettes, he hopes to describe the basic events that are coupled at equilibrium to the oxidation and reduction of common redox cofactors. Redox cofactors will be examined, both individually, and when integrated in multiple redox cofactor chain maquettes. The PI plans to activate intraprotein electron and radical transfer through these chains with light, oxygen or with electrical methods at the electrode/peptide monolayer interface. These maquettes are designed to ultimately access the kinetic factors that govern electron transfer and reveal how the equilibrium properties manifest themselves on the kinetic timescale.

描述：氧化还原酶功能障碍逐渐被认为是一种 对几种常见疾病的衰弱做出了重大贡献 非常复杂，治愈前景不佳。 了解 不同类别氧化还原酶的功能原理，以及 他们的工程公差和故障阈值几乎 肯定有助于改善疾病的影响 提供急需的诊断工具并指明方向 治愈。 该提案旨在理解的一个基本部分 许多氧化还原酶，即电子往返传递 催化或能量耦合位点。 PI 计划应用共识 以及从我们对天然氧化还原蛋白的检查中提取的一般性 从头构建和电子隧道功能设计 简化氧化还原蛋白的合成和组装；即模型。 通过检查相对简单的稳定中的天然氧化还原中心， 结构特征的异质肽环境 模型，他希望描述耦合的基本事件 常见氧化还原辅因子的氧化和还原平衡。 氧化还原辅助因子将被单独和整合时进行检查 在多个氧化还原辅因子链模型中。 PI 计划激活 蛋白质内电子和自由基通过这些链转移 光、氧气或在电极/肽上使用电方法 单层界面。 这些模型旨在最终访问 控制电子转移的动力学因素并揭示了如何 平衡特性在动力学时间尺度上表现出来。