Dynamics-Function Relationships of Glyoxalase I

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9600968 Stone The goal of the research is investigate the functional relevance of active site dynamics in the enzyme glyoxalase I (Glx I). Heteronuclear NMR relaxation data will be used to calculate parameters describing the internal motions on fast (ps-ns) and slower (-ms) time scales. Comparison of the free enzyme with the enzyme bound to reaction product and to transition state analog inhibitors will indicate the changes in active site dynamics that occur along the reaction coordinate of the enzyme-calatyzed reaction. The role of enzyme dynamics in controlling and limiting functional kinetics will be investigated by correlating the rates of Glx I catalytic turnover and of ligand association and dissociation with the millisecond time scale dynamics. The proposed educational activities involve formal teaching responsibilities at Indiana University as well as: (1) undergraduate biochemistry curriculum development; (2) graduate level molecular modeling workshops; (3) graduate education in written comprehension and expression of scientific ideas; (4) a practical course in NMR relaxation and dynamics analysis for NMR professionals; and (5) mentorship of graduate, undergraduate and high school students. %%% Enzymes are protein molecules that catalyze (increase the rate of) chemical reactions. They are involved in many important biochemical and industrial processes. The proposed research will investigate the motions that occur in enzyme molecules and the relationship between these motions and the function of the enzyme. In the long term such studies may enable us to design new enzymes or to design molecules. The proposed educational activities involve formal teaching responsibilities at Indiana University as well as: (1) assessment and modification of the undergraduate biochemistry curriculum to improve the preparation of students for their target careers; (2) use of manual and computerized model building as graduate level educational aids; (3) developme nt of graduate courses in the critical reading of research articles and the clear, concise written presentation of scientific ideas; (4) composition of a practical course for scientists interested in studying motions in proteins; and (5) mentorship of graduate, undergraduate and high school students including a specific focus on minority students. ***