Proton-Coupled Electron Transfer in Biomimetic Systems

仿生系统中的质子耦合电子转移

• 批准号: 7499138
• 负责人: DANIEL G. NOCERA
• 金额: $ 7万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7499138
• 关键词: Accounting; Active Sites; Address; Allosteric Regulation; Amino Acids; Area; Binding; Biochemical; Biological; Biological Models; Biology; Biomimetics; Bypass; Catalysis; Chemistry; Condition; Coupled; Coupling; Data; Deuterium; Electron Transport; Electrons; Enzymes; Escherichia coli; Event; Experimental Designs; Free Energy; Future; Generations; Hydrogen; Individual; Isotopes; Ketones; Kinetics; Lasers; Measurement; Measures; Methodology; Methods; Modeling; Molecular Biology Techniques; Monitor; Motion; Object Attachment; Optics; Oxidation-Reduction; Oxygen; Pathway interactions; Peptides; Photosensitizing Agents; Photosynthesis; Porphyrins; Positioning Attribute; Process; Property; Proteins; Proton Pump; Protons; RNA Splicing; Reaction; Research; Research Personnel; Respiration; Ribonucleotide Reductase; Ribonucleotide Reductase Subunit; Role; Sodium Chloride; Spectrum Analysis; Structure; Surface; System; Tail; Time; Transport Process; Tyrosine; Water; cofactor; design; electron donor; insight; knowledge of results; novel; professor; programs; protoporphyrin IX; response; small molecule

Proton-coupled electron transfer (PCET) is central to small-molecule activation processes, the function of redox-driven proton pumps and radical initiation and transport processes in biology. By examining PCET networks in model and natural systems, we aim to develop a mechanistic framework with which to interpret these processes. In doing so, we will contribute to an understanding of the structure/function relations of a variety of enzymes and proteins. This proposal seeks to elaborate PCET on three fronts: (1) The mechanism of PCET will be determined by undertaking time- resolved laser measurements on assemblies formed from a photoexcitable porphyrin donor (D) and acceptor (A) juxtaposed by a proton transfer interface (---[H+]---). The assemblies are designed to possess independent optical and vibrational signatures for electron and proton transfer events, thus allowing the fate of the proton in response to the electron and vice versa to be monitored by transient spectroscopies under a variety of conditions. These data and accompanying theoretical analysis will comprise a powerfully predictive framework for future interpretations of enzyme catalysis. (2) PCET will be studied in biological systems with the same mechanistic rigor that we have achieved in the foregoing model systems. The role of PCET in amino acid radical initiation and transport will be explored with the 35 A electron/proton coupled pathway in E. coli ribonucleotide reductase (RNR). Radicals will be generated from photoactive peptides or from non-natural amino acid photosensitizers, thereby bypassing the normal radical generation process originating at the diiron metallocofactor. The competency of these photoinitiated radicals at turning over RNR under various conditions (e.g., radical position along the pathway, variable effector and substrate concentrations) will be established using biochemical probes; the kinetics of radical transport will be investigated by transient laser spectroscopy. The combination of these steady-state and time-resolved studies should provide the most complete picture to date of PCET in a natural system. (3) The involvement of PCET in biological small molecule activation will be quantified with emphasis on bond-making and bond-breaking processes involving oxygen and water. PCET reactions will be investigated for protoporphyrin IX model cofactors that confine the delivery of protons and electrons in a face-to-face arrangement to bound O O bonds and assembled oxygen atoms derived from water. These studies will provide direct insight into the PCET processes that are the underpinning of photosynthesis and respiration.

质子耦合电子转移（PCET）是小分子激活过程的中心，是氧化还原驱动的功能 质子泵以及生物学中的根治性启动和运输过程。通过在模型和模型中检查PCET网络 自然系统，我们旨在开发一种机械框架来解释这些过程。这样，我们 将有助于理解多种酶和蛋白质的结构/功能关系。这 提案旨在在三个方面详细阐述PCET：（1）PCET的机制将通过进行时间来确定 - 由光电孔供体（D）和受体（a）形成的组件上解决的激光测量 由质子转移界面并列（--- [H+] ---）。这些组件的目的是具有独立的光学和 电子和质子转移事件的振动特征，从而使质子的命运响应于 电子，反之亦然，可以在各种条件下通过瞬态光谱监测。这些数据和 伴随的理论分析将构成一个有力的预测框架，用于将来解释 酶催化。 （2）PCET将在具有与我们具有相同机理的生物系统中进行研究 在上述模型系统中实现。 PCET在氨基酸自由基开始和运输中的作用将是 用35 A中的Elether/Proton耦合途径在大肠杆菌核糖核苷酸还原酶（RNR）中探索。激进分子将是 由光活性肽或非天然氨基酸光敏剂产生，从而绕过正常 源自二铁金属生产者的根本生成过程。这些光学激进分子的能力 在各种条件下翻转RNR（例如，沿途径的自由基位置，可变效应子和底物 浓度将使用生化探针建立；激进运输的动力学将由 瞬态激光光谱。这些稳态和时间分辨研究的结合应提供最多的 自然系统中PCET的完整图片。 （3）PCET参与生物小分子 激活将被量化，重点是建立键合和涉及氧气和水的键合过程。 将研究PCET反应的原源性IX IX模型辅助因子，该辅助因子限制质子的递送和 面对面排列的电子与o o键和源自水的组装原子。这些 研究将直接了解光合作用和呼吸的基础的PCET过程。