Design and Evolution of Inorganic Reactivity in Supramolecular Protein Scaffolds

有了这个奖项，化学部的生命过程计划的化学是支持博士F。Akif Tezcan和他的研究小组设计，工程师和进化具有金属基催化位点的超分子蛋白质组装体，用于水解和氧化还原转化。蛋白质是自然界中最重要的组成部分，可以用来构建复杂的生物机器，进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受到限制。这项研究利用了Tezcan实验室以前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装体，并显着改善酶功能。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开展外展工作，包括积极招募代表性不足的团体的成员进行研究，通过各种自发和校园支持的计划招募高中生，并参与当地小学的科学展览会。该项目是一个整合无机化学原理，蛋白质工程和分子生物学，研究和控制蛋白质自组装和无机反应。蛋白质结构单元经过适当设计，可组装成具有界面金属中心的规定超分子组装体。这些组件的物理，生物化学和催化性能的特点是由一套大的技术，包括蛋白质晶体学，溶液生物物理方法，酶活性测定，和各种方法在无机光谱。通过合理的重新设计和定向进化，这些组件的酶活性被微调和优化。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，并有助于阐明自然界如何进化蛋白质以利用和利用金属反应性。

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.