Tuning Redox Potentials of Metal Centers in a Single Protein

化学系的生命过程化学计划资助伊利诺伊大学香槟分校的Yi Lu博士研究蛋白质中金属中心的氧化还原电位与金属中心的二级配位球的依赖关系。这一努力很重要，因为蛋白质的氧化还原电位是许多化学和生物过程的核心属性，从光合作用和呼吸作用中的电子转移，到燃料电池的催化和固氮。尽管氧化还原电位很重要，但对控制蛋白质氧化还原电位的因素，特别是那些不干扰金属中心初级配位球的因素，仍然缺乏全面和系统的了解。这个项目将有助于填补这一知识空白；新知识将应用于解决化学和生物中有趣的问题。跨学科的研究将为学生的健康培养奠定基础。研究结果将纳入新的和现有的课程，并向广大受众进行介绍。这一研究项目将促进对影响蛋白质中金属中心氧化还原电势的因素的基本理解。这一新的认识将被应用于合成用于生化研究的新的水溶性、稳定的氧化还原试剂，这些试剂将被用于研究Marcus理论中倒置区域中的电子转移，以及其活性通过其氧化还原电位的变化来调节的生物催化剂。氧化还原电势被合理修饰的方法包括专门针对金属二配位球体的点突变，使用非天然氨基酸以天然氨基酸不可能改变的方式改变金属位置的空间和电子性质，以及蛋白质定向进化以提供相对较大序列空间的快速探索。

The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Yi Lu of University of Illinois at Urbana-Champaign to study the dependence of the redox potential of metal centers in proteins on the secondary coordination sphere of the metal center. This effort is important because the redox potential of proteins is a property at the heart of many chemical and biological processes, ranging from electron transfer in photosynthesis and respiration, to catalysis in fuel cells and nitrogen fixation. Despite the importance of redox potentials, a comprehensive and systematic understanding of factors that control the redox potentials of the proteins, particularly those factors that do not perturb the primary coordination sphere of the metal centers, remains elusive. This project will contribute to filling this knowledge gap; the new knowledge will be applied in addressing interesting problems in chemistry and biology. The interdisciplinary research will be a ground for the sound training of students. The results of the research will be integrated in new and existing courses and in presentations to a broad range of audiences. This research project will advance the fundamental understanding of the factors that affect the redox potential of metal centers in proteins. The new understanding will be applied in the synthesis of new water-soluble, stable redox agents for biochemical studies, which in turn will be used to study the transfer of electrons in the inverted regime of Marcus theory, and of biocatalysts whose activity is tuned by changes in their redox potential. The methods by which the redox potential will be rationally modified include point mutation directed exclusively to the second-coordination sphere of the metal, use of non-natural amino acids to change the steric and electronic properties of the metal site in ways not possible using natural amino acids, and protein directed evolution to afford the fast exploration of a relatively large sequence space.