CRYSTALLOGRAPHIC STRUCTURE ANALYSES OF PROTEIN/LIGAND COMPLEXES

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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. Beam time is requested for three crystallographic projects studying protein/ligand interactions. Rhodopsin is the G-protein coupled receptor (GPCR) involved in the first molecular steps in vision. Several specialized experiments for observing the conformational change leading to signal transduction for this protein are planned. These experiments will have considerable impact on drug design efforts for other GPCRs making up about a third of all current drug targets. Beam time will also be used for continued studies of streptavidin mutants to aid in understanding the tight binding of the protein and biotin. Synchrotron radiation is needed to study small crystals and obtain ultra-high resolution data sets for some of the streptavidin/biotin complexes. Finally, beam time is requested for glutathione S-transferase complexes and mutants yielding small crystals or high resolution diffraction patterns. These studies are aimed at understanding the mechanism and ligand binding properties of this drug detoxication enzyme.