X-Ray Diffraction Resource for Biochemical Sciences

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9317398 Rayment Funds are requested for an x ray area detector system that will be used to determine the structures of a wide variety of proteins at the University of Wisconsin, Madison. The instrument will be located at the Institute for Enzyme Research and will be used by seven laboratories on campus. These groups have crystallographic projects ready for x ray data collection and are currently limited by restricted access to the necessary instrumentation. To date, x ray crystallography is the most powerful technique for determining the accurate positions of atoms in proteins and macromolecular aggregates, and thus should be made available to all studies that are directed towards understanding the molecular basis of structure/function relationships. Due to major improvements in x ray data collection hardware and software, it has become possible, in recent years, for an increased number of investigators to conduct x ray crystallographic studies. As a consequence, it is now realistic and appropriate for these techniques to be incorporated into a wide range of research programs. At the University of Wisconsin there are currently seven groups who have obtained high quality protein crystals and need access to suitable x ray data collection hardware. The proteins under investigation in the above mentioned groups differ significantly in both their physical size and biological function. At one end of the spectrum, continued studies of myosin subfragment 1 will provide the structural information necessary for establishing the molecular basis of muscle contraction (Rayment). The combination of x ray crystallographic a nalyses with biochemical and kinetic approaches to study UDP galactose 4 epimerase, biotin carboxylase, and pyruvate kinase will provide a molecular framework for understanding the catalytic function of these enzymes, all of which proceed through different classes of chemical reactions (Cleland, Frey and Reed). Likewise, the proposed studies of peptide inhibitors bound to pepsin and similar enzymes will provide an opportunity to test and develop strategies for rational drug design (Rich). Finally, the application of NMR and very high resolution x ray crystallography to the study of electron transport proteins will yield unique insight into those structural factors that modulate oxidation reduction potentials and electron transfer rates (Holden and Markley). Although most of the investigators are specialized in other biochemical disciplines, they are all committed to using and supporting the instrumentation requested in this proposal. Indeed, they have already invested considerable time, effort, and personnel in the development of these crystallographic projects as complementary approaches to their research interests. At present, these programs are severely limited by the lack of access to suitable x ray data collection hardware. u ~ ~CRD0521TMP A ~MF240B TMP 7N ~CAL2B38TMP 2y ~CRD2523TMP 5y ~CAL0607TMP 9317398 Rayment Funds are requested for an x ray area detector system that will be used to determine the structures of a wid S U z | ! ! ! ! ! F S S ; CG Times Symbol & Arial 1 Courier 0 MS LineDraw h e e I = abstract Deseree King, BIR Deseree King, BIR