Mechanisms of Hydrogenase Function

该奖项由化学系生命过程化学项目资助埃默里大学的Brian Dyer博士研究生命系统如何利用质子耦合电子转移过程以化学键的形式高效储存能量。与化学键中的能量存储有关的最基本的电子和质子转移反应是那些涉及质子还原为分子氢的反应。尽管人造催化剂相对简单，但在加速这一过程方面并不是很有效。相比之下，生命系统进化出了一类名为氢酶的酶，这种酶能以非常快的速度催化质子还原为分子氢，而且能量损失很小。氢酶是理解多电子、多质子化学有效催化的基本原理的理想模型，这对于包括太阳能燃料的产生在内的广泛应用是重要的。虽然氢酶的结构已经很好地确定了，但它们的机制仍然知之甚少；事实上，尽管酶活性部位的化学结构已经在合成的模拟物中准确地复制出来，但这些模拟物作为催化剂失败了，这突显了围绕活性部位的蛋白质结构的重要性。戴尔团队使用独特的基于激光的方法来阐明电子和质子转移过程的动力学和机制，以及蛋白质在控制这些过程中的作用。这项研究帮助所有级别的学生发展高度跨学科的技能和专注于可再生能源科学的知识库。可再生能源科学方面的培训是通过埃默里化学实习生计划(高中生)和埃默里Sure and Sre计划(本科生)完成的，重点是从历史悠久的黑人亚特兰大大学中心招收的少数族裔学生。戴尔教授的实验室有传播尖端化学技术的良好记录，例如现在广泛应用于蛋白质折叠的激光诱导T-跳跃方法。氢化酶体现了高效氧化还原酶机制研究的内在挑战。这些挑战既是实际的，因为用kcat 1,000 S-1解决酶的分子过程是困难的，也是概念的，因为协调电子和质子转移反应的结构和动力学的复杂性。由于这些酶的催化速度非常快，因此很难直接研究它们的机制。戴尔实验室最近开发了一种方法，可以研究快速酶周转过程中的基本电子和质子转移步骤。该方法结合了激光诱导的氧化还原电位跳跃和酶活性部位的时间分辨红外光谱研究。使用这种独特的方法，他们研究了氢酶的关键机制问题，包括这些酶如何一起移动电子和质子以避免高势垒陷阱(测试电子中和性原理)，什么是质子途径以及质子转移和电子转移是如何控制的，以及分子氧与活性部位反应、酶失活和还原再激活的机制是什么。戴尔教授创造了独特的研究机会，在这项研究中广泛培训高中生、本科生和研究生，并帮助他们发展高度跨学科的技能，获得专注于可再生能源科学的知识库。该奖项反映了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 this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Brian Dyer from Emory University to investigate how living systems efficiently store energy in chemical bonds using proton coupled electron transfer processes. The most basic electron and proton transfer reactions relevant to energy storage in chemical bonds are those involved in the reduction of protons to molecular hydrogen. Man-made catalysts are not very efficient at accelerating this process, despite its relative simplicity. In contrast, living systems have evolved a class of enzymes called the hydrogenases that catalyze the reduction of protons to molecular hydrogen at extraordinary rates and with little energy loss. The hydrogenases serve as ideal models for understanding the basic principles of efficient catalysis of multi-electron, multi-proton chemistry, which is important for a wide range of applications including generation of solar fuels. While the structures of hydrogenases are well established, their mechanisms remain poorly understood; indeed, although the chemical structures of the active site of the enzymes have been exactly reproduced in synthetic mimics, these mimics fail as catalysts, highlighting the importance of the protein architecture that surrounds the active site. The Dyer group uses unique laser-based methods to elucidate the dynamics and mechanisms of the electron and proton transfer processes and the role of the protein in controlling them. This research helps students at all levels develop highly interdisciplinary skills and a knowledge base focused on renewable energy science. Training students in renewable energy science is accomplished through the Emory Chemistry Intern Program (high school students) and the Emory SURE and SIRE programs (undergraduates) with an emphasis on underrepresented minority students recruited from the Historically Black Atlanta University Center. Professor Dyer's laboratory has a strong record of dissemination of cutting edge chemical techniques such as the laser induced T-jump methods now widely used in protein folding.Hydrogenases exemplify the challenges inherent to mechanistic studies of the highly efficient oxidoreductases. These challenges are both practical, due to the difficulty of resolving the molecular processes for enzymes with kcat 1,000 s-1, and conceptual, due to the complexity of the structures and dynamics that orchestrate the electron and proton transfer reactions. Because of the extraordinarily fast catalytic rates of these enzymes, their mechanisms have been difficult to study directly. The Dyer lab recently developed an approach that enables the study of the elementary electron and proton transfer steps during fast enzyme turnover. The approach combines a laser-induced redox potential jump with time-resolved infrared spectroscopy studies of the enzyme active site. Using this unique approach, they investigate critical mechanistic questions for the hydrogenases, including how these enzymes move electrons and protons together to avoid high barrier traps (testing the principle of electroneutrality), what are the proton pathways and how are proton transfer and electron transfer gated, and what are the mechanisms of the reaction of molecular oxygen with the active site, enzyme inactivation, and reductive reactivation. Professor Dyer creates unique research opportunities to broadly train high school, undergraduate and graduate students in this research, and to help them develop highly interdisciplinary skills and gain a knowledge base focused on renewable energy science.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.