Our understanding of the mechanisms of proteins action has been derived from determination of the structures of the native proteins, protein-ligand complexes, and chemically-modified structures. This has come from a combination of chemical and physical methods, which have provided insight into the fundamentals of protein folding, the mechanism of enzyme action, and a host of other structures and processes. This, in turn, has led to a better understanding of the causes to be important in biomedical research. Amino acid side chain modification with functional groups reagents (Means and Feeney, 1971) can test the role of a particular side chain. For example, the cationic -amino group of lysine can be converted into an anionic or neutral group, probing the importance of the charge. The need for an amine group can be tested by converting it to the likewise cationic guanidinyl group. Dansyl chloride will convert the amino group to a near- uv chromophore used to monitor changes in the local environment. Spectroscopic methods provide information without causing chemical changes. Absorbance is useful for quantitative determination of any chromophore with a resolved absorption band. Changes in absorption spectra reflect changes in the environment of the chromophore (Timasheff and Gorbunoff, 1967; Kirtley and Koshland, 1972). Fluorescence provides more sensitive probes of local environments and useful measures of intramolecular distances (Stryer, 1978). Raman spectra, especially resonance Raman, contain information on local structure and changes related to function (Spiro and Gaber, 1977). This subproject is a continuation of work on snake venom hemorrhagic factor structure and the relationship between the structures so determined and the activity of the proteins. This will be enhanced by interaction with the molecular biology group here. The educational objective is to strengthen the experimental and theoretical background of the students and faculty involved in the program to better serve the health care needs of the community in the future. Students will learn techniques for use in future biomedical research. Those going into health professions (the majority of the undergraduates) will gain a better understanding of cellular and subcellular function, thus being better able to integrate the knowledge from the classroom with practical laboratory experience. The faculty will be better trained to educate future students as well as keeping current with the latest developments in the biomedical sciences.
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