X-ray crystallography is the most powerful and efficient method for the determination of macromolecular structures at atomic resolution. Three- dimensional graphical representation and analysis of structure provides a critical means to relate molecular fold and function. To expand its research efforts in structural biology, Finch University of Health Sciences/The Chicago Medical School has recently hired its first crystallographer faculty member. This action has stimulated the organization of a core structural community designed to address the needs of the new investigator, as well as the goals of existing NIH funded research faculty. Therefore, the PI. requests resources to purchase core X-ray instrumentation, as well as additional support items, dedicated to the establishment of a shared facility. In the event that this proposal is approved, the University will commit funds comparable to the original purchase price of the requested instrumentation to provide for the long-term maintenance and technical support of this facility (>5 years). The PI. is a junior crystallographer in the Department of Biochemistry and Molecular Biology, the home department to most core users. The P.I.'s research uses crystallography to study the fold and mechanisms of small RNA enzymes, such as the hairpin ribozyme. Other investigators study the mechanism and inhibition of enzymes from human pathogens, such as: HIV protease, PPi-dependent PFK from Borrelia, and the gp63 surface protease from Leishmania. Additional researchers are pursuing the crystallization o integral membrane proteins, such as the mitochondrial citrate transporter and the soluble domains of nerve growth factor-receptor complexes. A final project involves a mutagenic/functional analysis of the F1-ATP synthase. The proposed crystallography core facility will complement existing research techniques that include: mutagenesis, kinetics, EPR, CD spectroscopy, surface plasmon resonance, and genetics. Establishment of a core crystallographic facility will enhance the productivity of University researchers by providing an essential resource to accomplish their NIH funded research. Such work has practical applications to human diseases in terms of diagnosis, prevention, and therapeutic development.
