Funds are requested for the acquisition of an area detector data collection system for macromolecular X-ray crystallography. This system would serve the needs of four structural biology groups in the Rosenstiel Basic Medical Sciences Research Center at Brandeis University. Together these groups have almost fifty people carrying out diffraction studies on biological macromolecules ranging from small proteins to intact muscle fibers. Over sixty different crystal systems are under study. The projects range in scope from de nova solution of crystal structures to study of mutant proteins generated by site-directed mutagenesis to direct observation of enzyme-substrate and -intermediate complexes by low-temperature X-ray crystallography to mapping of the entire binding surface of crystalline macromolecules by structure determination in organic solvents. These projects have significance for many areas of human health. For example, work on muscle protein components is of great importance for understanding and treating neuromuscular diseases. Mapping of binding surfaces is significant for the rational design of drugs. Studies on insulin and aldose reductase are providing crucial information for the design of more effective treatments for both Type I and Type II diabetes. These are just a few examples; nearly all of the projects are directly health-related. The equipment requested is a rotating anode generator with a high brilliance 0.3 mm focal spot, an imaging plate area detector equipped with focusing mirror optics, and cryo system to allow data collection at very low temperatures. This equipment is essential for many of the projects where the crystals are small and/or the unit cell is very large and the crystals are radiation sensitive. The requested equipment will allow us to carry out projects that are not feasible with our current facilities for data collection. Moreover, in certain cases, the availability of the new equipment will greatly facilitate the completion of projects that are now moving very slowly.
