This award supports a 12 month Japan Society for the Promotion of Science Postdoctoral Fellowship for Dr. Diane Peapus, Department of Biochemistry, Case Western Reserve University, at the Department of Chemistry, Kyoto University, Kyoto, Japan. Dr. Peapus will work with Professor Kunio Miki on a research project entitled, `Crystallographic Studies of Physiologically Important Enzymes.` The project aims to identify the structural basis for the biological function of key enzymes in important metabolic pathways using protein structures determined by X-ray crystallography. Two enzymes, metapyrocatechase and famesyl pyrophosphate (FPP) synthase, will be examined. The structure of the native enzyme along with the structures of bound forms will give information on 1) protein/substrate and protein/inhibitor binding interactions, 2) the geometry of the active site iron atom in bound and unbound states, 3) a molecular rationale for substrate specificity, and 4) mutations and/or conditions which would possibly relax substrate specificity or enhance detoxification. These studies will broaden our general understanding of the relationshop between the structure and function in biological mechanisms and open the way for possible intervention in regulating these pathways by either genetic, pharmaceutical, or chemical methods. The proposed research addresses a fundamental concern in the field of chemistry and the participants are well-matched for a cooperative effort. As Professor Miki is a recognized expert in the research area and Dr. Peapus has had considerable experience in the research techniques to be used, it is expected that both participants will benefit from the exchange. As such, the research satisfies the objectives of the program in its emphasis on the exchange and transfer of scientific knowledge through international collaboration.
