FUNDAMENTALS OF BIOLOGICAL ELECTRON TRANSFER

描述：(申请人提供)每个月都会带来新的发现和结构特征，这些蛋白质负责生物能量。 转化和化学转化与调控。我们的建议旨在 更好地理解生物学分子机制的基本原理 氧化和还原是这些蛋白质运行的基础，以及 为了揭示氧化还原酶的自然工程和结构， 支持这些进程。这样的理解应该为认识氧化和还原的正常工作范围提供实际的蓝图 功能，对压力挑战的容忍度，以及 失败和发病机制，以及提出补救的可能性。 天然氧化还原酶的计算与实验分析 具有分子结构和确定的功能，被用来开发 可应用于以下方面的机械性见解和工程指南 一般都是氧化还原酶。然后从头开始的氧化还原蛋白被设计用来揭示 与此相适应的蛋白质结构的基本结构方面 工程学。这些最小的模型蛋白质，maquettes，被证明是新的 揭示汽车本质结构-功能关系的车辆 隧道效应和耦合反应通常在高度复杂的情况下被掩盖 天然蛋白质。模型的设计和合成将包含 天然氧化还原酶中常用的氧化还原辅因子链 电子进出底物氧化还原的酶位置。 将开发将氧化还原辅因子附近的底物结合到 进行简单的多电子催化。我们主要集中在亚铁血红素，黄素 和氧化还原活性氨基酸，如色氨酸、酪氨酸和半胱氨酸 具有代表性的隧道链活性元件和广泛的 催化位作用和化学作用。黄素为双电子 辅因子/底物用于研究更复杂的机制 在稳定底物的催化下发现的氧化还原反应。核磁共振和X射线 衍射揭示了产生函数的结构基础 结合在这些简单的蛋白质中。电子转移与多电子 催化反应将通过光和电方法激活，并 在溶液和As中用分光光度和电测法进行分析 电极表面的结构单层膜对热力学的剖析 电子和质子转移的动力学步骤。模型，稳定的和 可通过设计进行调整，有助于开发生物传感器和其他 分子装置。

DESCRIPTION: (provided by applicant) Each month brings new discovery and structural characterization of the proteins responsible for biological energy conversion and chemical transformation and regulation. Our proposal aims to better understand the fundamentals of the molecular mechanisms of biological oxidation and reduction that are basic to the operation of these proteins, and to uncover the natural engineering and architecture of oxidoreductases that support these processes. Such understanding should provide practical blueprints for recognizing the normal operating ranges of oxidative and reductive function, the tolerances to the challenge of stress, and the thresholds of failure and pathogenesis, as well as suggesting possibilities for remediation. Computational and experimental analysis of natural oxidation-reduction enzymes with molecular structures and identified function, are used to develop mechanistic insights and engineering guidelines that can be applied to oxidoreductases in general. Then de novo redox proteins are designed to uncover the essential structural aspects of protein architecture that accommodate this engineering. These minimal model proteins, maquettes, prove to be novel vehicles that reveal the essential structure-function relationships of tunneling and coupled reactions that are often obscured in highly complex natural proteins. Maquettes will be designed and synthesized to incorporate the chains of redox cofactors commonly used in natural oxidoreductases to lead electrons to and from enzymatic sites of substrate oxidation-reduction. Maquettes will be developed that bind substrates near redox cofactors to perform simple multi-electron catalysis. We focus principally on heme, flavin and redox-active amino acids such as tryptophan, tyrosine and cysteine as representative active elements of tunneling chains and a wide range of catalytic site actions and chemistries. Flavin as a two electron cofactor/substrate is used to investigate the mechanisms of the more complex redox reactions found in the catalysis of stable substrates. Nmr and x-ray diffraction reveal the structural foundations that give rise to the functions incorporated in these simple proteins. Electron transfer and multi-electron catalytic reactions will be activated by light and electric methods and analyzed by spectrophotometric and electrometric methods in solution and as structured monolayer films on electrode surfaces to dissect the thermodynamic and kinetics steps of electron and proton transfer. Maquettes, stable and adaptable by design, lend themselves to the development of biosensors and other molecular devices.