This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The formation of carbohydrate-protein complexes is important in a variety of processes involving the interaction of a cell with its environment. These processes include natural ones such as cell differentiation, cell aggregation, and cell signaling; they also include disease processes such as viral infection, malignancy, and unwanted inflammation. The development of drugs to moderate natural processes and inhibit disease processes begins with accurate structural models for the protein and for the oligosaccharide-protein interactions. NMR methods provide a potential source of these models, but a prerequisite is assignment of resonances to specific sites both within the protein and within the oligosaccharide. This has been particularly difficult for the large, difficult to express, proteins involved in carbohydrate processing. A good example of such a protein is the sialyltransferase, ST6Gal I, described in subproject 0007. We are developing a novel approach that links NMR resonances with mass spectrometry (MS) fragment identification through amide proton exchange rates measured by both methods. This work is beginning with applications to simple model proteins, but will eventually target ST6Gal I and other glycosyltransferases involved in cell-surface oligosaccharide synthesis.
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