Tuning Redox Potentials of Metal Centers in a Single Protein

调节单一蛋白质中金属中心的氧化还原电位

• 批准号: 1413328
• 负责人: Yi Lu
• 金额: $ 50万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413328&HistoricalAwards=false
• 关键词: Tuning; Redox; Potentials; Metal; Centers

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.

化学系的生命过程化学项目正在资助伊利诺伊大学厄巴纳-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圈的依赖性。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，从光合作用和呼吸中的电子转移到燃料电池和固氮中的催化作用。尽管氧化还原电位的重要性，一个全面和系统的理解的因素，控制蛋白质的氧化还原电位，特别是那些因素，不干扰的主要协调领域的金属中心，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的有趣问题。 跨学科的研究将成为学生良好训练的基础。研究结果将纳入新的和现有的课程，并在介绍给广大观众。该研究项目将推进对影响蛋白质中金属中心氧化还原电位的因素的基本理解。新的理解将被应用于合成新的水溶性，稳定的氧化还原剂的生化研究，这反过来将被用来研究电子的转移在马库斯理论的倒置制度，和生物催化剂的活性是由他们的氧化还原电位的变化调整。 氧化还原电位将被合理地修改的方法包括专门针对金属的第二配位领域的点突变，使用非天然氨基酸以使用天然氨基酸不可能的方式改变金属位点的空间和电子性质，以及蛋白质定向进化以提供相对大的序列空间的快速探索。

项目成果

A Purple Cupredoxin from Nitrosopumilus maritimus Containing a Mononuclear Type 1 Copper Center with an Open Binding Site

• DOI: 10.1021/jacs.5b13128
• 发表时间: 2016-05-25
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Hosseinzadeh, Parisa;Tian, Shiliang;Lu, Yi
• 通讯作者: Lu, Yi

Long-Range Electron Transfer in Engineered Azurins Exhibits Marcus Inverted Region Behavior

• DOI: 10.1021/jz5022685
• 发表时间: 2015-01-01
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY LETTERS
• 影响因子: 5.7
• 作者: Farver, Ole;Hosseinzadeh, Parisa;Pecht, Israel
• 通讯作者: Pecht, Israel