This proposal requests funds for purchase of a new X-ray data collection system to serve as the primary data collection instrument for macromolecular crystallography at the University of California, Irvine. The current system is 11 years old and has a high yearly cost to maintain. Even though synchrotron data collection is extensively used by the UCI community, there is still the need for a reliable in house system to screen crystals prior to synchrotron trips, search for heavy atom derivatives, and in some cases solve structures using in house data. Our goal is to replace the older system with a highly reliable system that is inexpensive to run. We propose to purchase a Bruker X8 Prospector CCD system equipped with a Incoatec microfocus sealed, air- cooled x-ray tube and 2D Montel multilayer mirrors. Since this system uses a sealed tube the X-ray source is essentially maintenance free as opposed to a rotating anode. We expect the yearly cost of operation to drop form ~$30,000 per year to ~$5,000 per year. There are 5 Major Users (Goulding, McPherson, Tsai, Poulos, and Sevrioukova) four of whom are funded by NIH grants. Dr. Goulding has been at UCI for only one year and will be applying for NIH support. Since 1992 when Prof. Poulos was recruited to UCI to initiate the development of structural biology at UCI, structural biology has substantially expanded. There are now 6 faculty crystallographers, 2 NMR spectroscopists, and 3 computational structural biologists with one more tow join UCI this summer. Given that crystallographic software, data collection, and crystallization have become much more user-friendly, the scope of crystallographic projects also has extended to many other labs that are not formally crystallographic labs. Dozens of protein, enzyme, virus and antibody structures have been solved, and the results have led to new molecule design and synthesis and animal model tests. Therefore, while this proposal has 5 primary users, there are 6 other faculty labs that also use the current system many of whom are funded by NIH grants. The requested equipment will provide the primary on site data collection system for 10 individual NIH funded projects.
Crystal structures of important health related proteins under investigation in the labs of the Major Users provide essential information for understanding function. The structural organization of the viral genome (McPherson), the structural biology of antibiotic biosynthesis (Tsai) the structural biology of TB drug targets (Goulding), structure based inhibition of nitric oxide synthase (Poulos) and mechanisms of apoptosis (Sevrioukova) all have clearly defined health related significance.
