Tuning Redox Potentials of Metal Centers in a Single Protein

化学学部的生命过程化学项目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对金属中心二级配位球的依赖性。这项工作很重要，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，到燃料电池中的催化作用和固氮作用。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的全面和系统的了解仍然难以捉摸。该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学中有趣的问题。跨学科的研究将为学生的良好训练奠定基础。研究的结果将纳入新的和现有的课程，并向广泛的听众介绍。本研究项目将促进对影响蛋白质中金属中心氧化还原电位的因素的基本认识。新的认识将应用于合成新的水溶性、稳定的氧化还原剂用于生化研究，而这些氧化还原剂又将用于研究马库斯理论中的电子转移，以及通过其氧化还原电位的变化来调节活性的生物催化剂。合理修饰氧化还原电位的方法包括只针对金属的第二配位球的点突变，使用非天然氨基酸来改变金属位点的空间和电子性质，这是使用天然氨基酸无法做到的，以及蛋白质定向进化以提供对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.