Upgrade of Macromolecular X-ray Diffraction Facilities

DESCRIPTION (provided by applicant): The Kahlert Structural Biology Center (KSBL) at the University of Minnesota, was formed in 1989 as a resource for macromolecular X-ray crystallography. Currently there are 14 major users, with 20 identified future users, covering 12 different departments, 2 campuses and 2 external universities. At this time, it is the only such facility in the State of Minnesota. The KSBL houses two data collection systems; (1) a BrukerAXS Hi-Star system, which has been superceded many times, and is currently non-operational, and (2) an R-axis IV++ system, whose detector and optics are state-of-the-art, but are coupled with a 14 year old X-ray generator and water chiller that are having increasing problems due to age. In this proposal, funds are requested to upgrade the Hi-Star system with another R-axis IV++ system, but utilizing a new X-ray generator, the MicroMax-007, which is optimized for small crystals giving 2 to 2.5-fold increased X-ray flux over our current R-axis IV++ system (optimized for medium to large sized crystals). In comparison to the present Hi-Star system, crystals will experience up to a 10-fold increase in X-ray flux, and data from crystals with cell dimensions between 250-700A can be collected on the proposed instrumentation. Currently 80% of the crystals in the KSBL would benefit from the increased flux of the new system, and 6 projects have unit cells too large to be collected on the Hi-Star. If this application is successful, the University of Minnesota has pledged $150,000 in matching funds to replace the X-ray generator and water chiller on our second system, and to contribute to service contracts on the equipment. The KSBL has made important contributions to understanding the molecular basis of processes important to biomedical science, resulting in 133 publications. These research areas include lipid/protein interactions, metalloenzymes, iron storage proteins, citric acid cycle enzymes, microbial toxins, microbial virulence, viral DNA packaging, metabolic control of enzymes and amino acid derived cofactors. The majority of the funding that supports these research areas is provided through grants from the National Institutes of Health.