RUI: The Role of Protein Dynamics in Catalysis and Subunit Cooperativity

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This research will advance our understanding of how the dynamic properties of proteins play a critical role in the enzymes involved with the integration of protein, carbohydrate, and fat metabolism. The project will investigate the linkage between dynamic protein structure and both catalysis and the regulation of activity in three enzymes that play central roles in metabolism: glutamate dehydrogenase, malate dehydrogenase, and 3 phosphoglycerate dehydrogenase. Communication between subunits affecting catalysis and substrate binding regulate each of these enzymes. The roles of individual side chains in catalysis or in communication between subunits will be probed using site-specific mutations. The effects of mutations will be studied by functional assays, structural analysis using X ray crystallography and mass spectrometry, and computational approaches. The hypothesis that both catalytic activity and biological regulation involve changes in the dynamic properties of the protein will be directly tested by engineering flexibility changes in various regions of the protein and correlating the effects with alterations in both activity and subunit communication. Broader Impacts: The research is integrated fully into the education of undergraduates. Students will work on individual research projects, take laboratory courses with the research embedded into the course, or may take a research-based course for non-science majors. Students are integrally involved in the design of experiments, conduct of the research, and data analysis and presentation. Students become involved in their first year and often follow the research for 2-3 years. The research brings both a quantitative and physical understanding of biological processes to the participating students. They also participate in outreach to area elementary schools to bring the excitement of science to local children and their teachers. Students engaged in the project are drawn from the University of Richmond and Virginia State University.