X-Ray Diffraction Resource for Biochemical Sciences

9317398美国威斯康星大学麦迪逊分校要求提供一套x射线区域探测器系统的资金，该系统将用于确定多种蛋白质的结构。该仪器将放置在酶研究所，并将由校园内的七个实验室使用。这些小组已经为x射线数据收集准备好了晶体学项目，但目前由于限制使用必要的仪器而受到限制。迄今为止，x射线晶体学是确定蛋白质和大分子聚集体中原子精确位置的最强大的技术，因此应该用于所有旨在了解结构/功能关系的分子基础的研究。由于x射线数据采集硬件和软件的重大改进，近年来，越来越多的研究人员可以进行x射线晶体学研究。因此，现在将这些技术纳入广泛的研究计划是现实和适当的。在威斯康星大学，目前有七个小组已经获得了高质量的蛋白质晶体，并且需要获得合适的x射线数据收集硬件。上述各组所研究的蛋白质在物理大小和生物学功能上都有显著差异。一方面，对肌球蛋白亚片段1的持续研究将为建立肌肉收缩的分子基础提供必要的结构信息（Rayment）。结合x射线晶体学分析与生化和动力学方法研究UDP半乳糖4 epimase，生物素羧化酶和丙酮酸激酶将为理解这些酶的催化功能提供一个分子框架，所有这些酶都通过不同类型的化学反应进行（Cleland， Frey和Reed）。同样，对胃蛋白酶和类似酶结合的肽抑制剂的研究将提供一个测试和开发合理药物设计策略的机会（Rich）。最后，核磁共振和非常高分辨率的x射线晶体学应用于电子传递蛋白的研究将对那些调节氧化还原电位和电子传递速率的结构因素产生独特的见解（Holden和Markley）。虽然大多数研究人员都是其他生化学科的专业人员，但他们都致力于使用和支持本提案中要求的仪器。事实上，他们已经投入了大量的时间、精力和人员来开发这些晶体学项目，作为他们研究兴趣的补充方法。目前，由于缺乏合适的x射线数据采集硬件，这些程序受到严重限制。u ~ ~CRD0521TMP A ~MF240B TMP 7N ~CAL2B38TMP 2y ~CRD2523TMP 5y ~CAL0607TMP 9317398经费申请用于x射线区域探测器系统，该系统将用于确定一个宽的结构S U z b|!!!!!F是s；CG时代符号& font； Arial 1 Courier 0 MS line = abstract Deseree King, BIR Deseree King， BIR

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