The overall objective of the proposed research is to understand the structure-taste relationship of molecules which share the biological property of tasting sweet, that is, which interact with the sweet taste receptor. Practically all the known compounds which are known to act as specific sweet taste stimuli in man are small molecules. Comparison of these small molecules suggests no obvious structural elements which may be responsible for the sweet taste. There are so far three taste active proteins known and we plan to determine the three-dimensional structure of two of them, Monellin and Miraculin. Monellin is a sweet tasting protein with no carbohydrates, and Miraculin is a taste modifying glyco-protein. Our specific goals are to determine the structures of these two proteins by X-ray crystallographic techniques. In contrast to the high flexibility of small molecules, these two proteins can be considered as "immobilized" ligands to the sweet receptors, and their three-dimensional structures will reveal the stereochemical arrangement of the functional groups which may be recognized by sweet receptors, and are likely to provide important insights into the understanding of the mechanism of taste perception, and help design compounds having beneficial pharmacological properties for diabetic patients.