Mechanisms of Hydrogenase Function

氢化酶功能机制

• 批准号: 2108290
• 负责人: Brian Dyer
• 金额: $ 45万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108290&HistoricalAwards=false
• 关键词: Mechanisms; Hydrogenase; Function

With support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Brian Dyer of Emory University will study how hydrogenase enzymes work to catalyze the interconversion of protons and hydrogen, thereby very efficiently producing molecular hydrogen, itself an important fuel. Indeed, this enzyme-catalyzed reaction is perhaps the most basic electron and proton transfer reaction relevant to molecular fuel production. In biological systems, this interconversion takes place with extraordinary rates and little energy loss. The hydrogenases will serve as ideal models for understanding the basic principles of efficient catalysis of multi-electron, multi-proton chemistry for generation of solar fuels. Storing solar energy in molecular fuels requires new catalysts that can efficiently perform chemistry that involves several electrons and protons to generate high-energy, chemical bonds. While the structures of hydrogenases are known, their mechanisms remain poorly understood. Also, the structure of the metal active sites in hydrogenases has been exactly reproduced in some synthetic model complexes but these complexes have failed as catalysts, which highlights the importance of the protein architecture that surrounds the active site of the hydrogenases. The results of this research on the hydrogenases can inform the design of better catalysts for making solar fuels. The research will provide an opportunity to broadly train students in an interdisciplinary setting, pursuing questions that are relevant to renewable energy science.A key challenge in studying hydrogenase enzymes lies in elucidating the mechanistic basis for the high catalytic efficiency of these oxidoreductases. There are both practical questions here, due to the difficulty of resolving the molecular processes for enzymes with kcat 1000 s-1, and conceptual questions, due to the complexity of the structures and dynamics that orchestrate the electron and proton transfer reactions. In this work, the Dyer research team will develop a general methodology for the study of fast electron and proton transfer reactions and a framework for understanding proton coupled electron transfer (PCET) in the oxidoreductases. The newly developed methods will be general and in principle could be applied to any catalytic redox reaction. The fundamental mechanistic questions to be answered for the hydrogenases are also relevant for the broader class of oxidoreductases, particularly for those enzymes that activate small and stable molecules, such as CO dehydrogenase and nitrogenase, which catalyze the multi-electron reduction of carbon dioxide and nitrogen, respectively. The research is expected to contribute to the elucidation of fundamental factors that control low-barrier proton and electron flow and provide a foundation for understanding PCET mechanisms in enzymes and in synthetic catalysts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系生命过程化学（CLP）项目的支持下，埃默里大学的Brian Dyer教授将研究氢化酶如何催化质子和氢的相互转化，从而非常有效地产生氢分子，氢本身就是一种重要的燃料。事实上，这种酶催化的反应可能是与分子燃料生产相关的最基本的电子和质子转移反应。在生物系统中，这种相互转化的速度非常快，能量损失很小。氢化酶将成为理解多电子、多质子化学高效催化太阳能燃料生成基本原理的理想模型。将太阳能储存在分子燃料中需要新的催化剂，这种催化剂可以有效地进行涉及多个电子和质子的化学反应，从而产生高能量的化学键。虽然氢化酶的结构是已知的，但其机制仍然知之甚少。此外，氢化酶中金属活性位点的结构在一些合成的模型配合物中得到了精确的复制，但这些配合物不能作为催化剂，这突出了围绕氢化酶活性位点的蛋白质结构的重要性。这项关于氢化酶的研究结果可以为设计更好的太阳能燃料催化剂提供信息。这项研究将提供一个机会，在跨学科的环境中广泛训练学生，追求与可再生能源科学相关的问题。研究氢化酶的一个关键挑战在于阐明这些氧化还原酶高催化效率的机制基础。这里既有实际问题，因为很难用kcat 1000 s-1解决酶的分子过程，也有概念问题，因为协调电子和质子转移反应的结构和动力学的复杂性。在这项工作中，Dyer研究小组将开发一种研究快速电子和质子转移反应的通用方法，并建立一个理解氧化还原酶中质子偶联电子转移（PCET）的框架。新开发的方法具有通用性，原则上可应用于任何催化氧化还原反应。要回答的氢化酶的基本机制问题也与更广泛的氧化还原酶有关，特别是那些激活小而稳定分子的酶，如CO脱氢酶和氮酶，它们分别催化二氧化碳和氮的多电子还原。该研究将有助于阐明控制低势垒质子和电子流的基本因素，并为理解PCET在酶和合成催化剂中的机制奠定基础。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。