This broadly titled research project represents a continuing effort to understand and correlate structure and biological function of proteins and glycoproteins. For the current 5-year period, of which the last 21 months are covered by this application, a central focus of the project has been derived from the recent definition of the many posttranslational modifications of protein, through which the 20 genetically coded primary amino acids give rise to the many hundred different derivatized amino acids actually found in proteins.
Specific aims for the current period have consequently been to elucidate the biological roles of posttranslational modificaions, concentrating on the following questions and systems: I. The biological roles of the glycosyl moieties in glycoproteins based on the fundamental hypothesis that there exists a universal """"""""language"""""""" of cell-cell and cell-molecule communication based on specific lectin-oligosaccharide interactions; II. The specificity determinants in in vivo modification of specific proteins (N-terminal modification of pancreatic Alpha-amylase and muscle enolase, and Eplison(Gamma-glutamyl)-lysine cross-link formation catalyzed by transglutaminase); III. The relation of primary structure to subunit interaction, metal binding and active site structure and specificity determinants for the various processing enzymes involved in posttranslational modificaion. The problems will be tackled primarily by establilshed methods, some of which have been developed in the past through work supported by this grant, but the exploration of new methodology will continue to be a significant component of this project. I also intent to continue to explore the direct application of new knowledge in the 3 proposed problem areas to such important practical problems as enzyme stabilization and protection for enzyme replacement therapy and the role of lectin-saccharide interactions in host-parasite or host-symbiote interactions in normal and pathological conditions.
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