Design and Evolution of Inorganic Reactivity in Supramolecular Protein Scaffolds

超分子蛋白支架中无机反应性的设计与演化

• 批准号: 1607145
• 负责人: Faik Tezcan
• 金额: $ 64万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1607145&HistoricalAwards=false
• 关键词: Design; Evolution; Inorganic; Reactivity; Supramolecular

With this award, the Chemistry of Life Processes Program of the Chemistry Division is supporting Dr. F. Akif Tezcan and his research group to design, engineer and evolve supramolecular protein assemblies with metal-based catalytic sites, for hydrolytic and redox transformations. Proteins are nature's premier building blocks for constructing complex biological machines that carry out normally challenging biochemical reactions. Examples are the light-driven water oxidation in photosystem II and nitrogen fixation in nitrogenases. The ability of chemists to control the assembly of proteins or to use them as synthetic building blocks has been limited. This research capitalizes on a protein design strategy developed previously in the Tezcan Lab (Metal-Templated Protein Interface Redesign). The project is designing and synthesizing protein assemblies, containing zinc and copper, with significantly improved enzymatic function. This project provides an expansive training ground for postdoctoral, graduate, undergraduate, and high school researchers in inorganic coordination chemistry, molecular biology, protein biochemistry, biophysical methods and computational protein design. The PI is undertaking outreach efforts on several different fronts, including active recruitment of members of underrepresented groups for research, recruitment of high school students through various self-initiated and campus-supported programs and involvement in science fairs at local elementary schools.The project is an integration of inorganic chemistry principles, protein engineering and molecular biology to study and control protein self-assembly and inorganic reactivity. Protein building blocks are properly designed to assemble into prescribed supramolecular assemblies with interfacial metal centers. Physical, biochemical and catalytic properties of these assemblies are characterized by a large suite of techniques including protein crystallography, solution biophysical methods, enzyme activity assays, and various methods in inorganic spectroscopy. The enzymatic activities of these assemblies are fine-tuned and optimized by rational re-design as well as directed evolution. The proposed studies establish the viability and scope of proteins as building blocks for synthetic chemistry, and help elucidate how nature may have evolved proteins to utilize and harness metal reactivity.

有了这个奖项，化学部门的生命过程化学项目支持F. Akif Tezcan博士和他的研究小组设计、制造和发展具有金属基催化位点的超分子蛋白质组件，用于水解和氧化还原转化。蛋白质是自然界构建复杂生物机器的首要基石，这些生物机器执行通常具有挑战性的生化反应。例如光系统II中的光驱动水氧化和固氮酶中的固氮。化学家控制蛋白质组装或将其用作合成构件的能力一直受到限制。这项研究利用了先前在Tezcan实验室开发的蛋白质设计策略（金属模板蛋白质界面重新设计）。该项目正在设计和合成含有锌和铜的蛋白质组件，具有显著改善的酶功能。该项目为无机配位化学、分子生物学、蛋白质生物化学、生物物理方法和计算蛋白质设计方面的博士后、研究生、本科生和高中研究人员提供了广阔的培训基地。PI正在几个不同的方面进行拓展工作，包括积极招募代表性不足的群体成员进行研究，通过各种自发和校园支持的项目招募高中生，以及参与当地小学的科学展览。该项目将无机化学原理、蛋白质工程和分子生物学相结合，研究和控制蛋白质的自组装和无机反应性。蛋白质构建块被适当地设计成具有界面金属中心的规定超分子组件。这些组合物的物理、生化和催化性质通过大量的技术来表征，包括蛋白质晶体学、溶液生物物理方法、酶活性测定和无机光谱中的各种方法。这些组合的酶活性通过合理的重新设计和定向进化进行微调和优化。拟议的研究确立了蛋白质作为合成化学基石的可行性和范围，并有助于阐明大自然如何进化出蛋白质来利用和利用金属的反应性。