Factors Influencing the Local Dynamics of Redox Metalloproteins

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This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Bruce Bowler at the University of Montana to carry out fundamental studies on the relationship between the conformational dynamics of metalloproteins and their functions, using cytochrome c as a model system. Cytochrome c is involved in electron transfer chemistry related to energy production in living cells. It also mediates programmed cell death. The heme of this protein sits in a crevice near the surface of the protein and the opening and closing of this crevice is believed to play a role in its function. The dynamics of heme crevice opening are observed using electron transfer reactions with inorganic compounds and also through the binding of small molecules to the iron atom of the heme. Mutations of amino acids adjacent to the heme crevice are being used to test the effect of local structural stiffness on the dynamics of the heme crevice. Mutations, which affect the stability of portions of the protein outside of the heme pocket, are also being used to test the effect of more distant parts of the protein structure on the dynamics of the functionally important heme crevice. This research grant provides training for graduate students and postdoctoral fellows thus enhancing our research infrastructure by growing the pool of trained scientists. The University of Montana enrolls 8% minority students, half of whom are Native Americans, and the Department of Chemistry & Biochemistry hosts an NSF-sponsored Research Experiences for Undergraduates program that recruits heavily from tribal colleges in Montana. Thus, underrepresented minorities are expected to participate in this research. Understanding the factors that control protein dynamics and thus function will provide a base of knowledge that will permit rational manipulation of protein function, allowing design of proteins with both optimized and novel activities with potential importance for industrially-important chemical transformations. For cytochrome c, specifically, this knowledge could be used to design components for molecular electronics devices.