Design and Evolution of Inorganic Reactivity in Supramolecular Protein Scaffolds

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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.