Mechanisms of Hydrogenase Function

在化学系生命过程化学(CLP)计划的支持下，埃默里大学的Brian Dyer教授将研究氢酶如何催化质子和氢的相互转化，从而非常高效地生产分子氢，而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，这种相互转化发生的速度非常快，能量损失很小。氢酶将成为理解多电子、多质子化学有效催化产生太阳能燃料的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执行涉及几个电子和质子的化学，以产生高能的化学键。虽然氢酶的结构已为人所知，但其机制仍然知之甚少。此外，氢酶中金属活性中心的结构在一些合成的模型络合物中得到了准确的再现，但这些络合物作为催化剂失败了，这突显了围绕氢酶活性中心的蛋白质结构的重要性。对氢酶的研究结果可以为设计更好的太阳能燃料催化剂提供依据。这项研究将提供一个机会，在跨学科的背景下广泛培训学生，探索与可再生能源科学相关的问题。研究氢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，由于用kcat 1000 S-1解决酶的分子过程的困难，也有概念性问题，由于协调电子和质子转移反应的复杂结构和动力学。在这项工作中，戴尔研究小组将开发研究快速电子和质子转移反应的一般方法，以及理解氧化还原酶中质子耦合电子转移(PCET)的框架。新开发的方法将是通用的，原则上可以应用于任何催化氧化还原反应。氢酶需要回答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的分子的酶，如CO脱氢酶和固氮酶，它们分别催化二氧化碳和氮气的多电子还原。这项研究有望有助于阐明控制低势垒质子和电子流动的基本因素，并为理解酶和合成催化剂中的PCET机制提供基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.