X RAY GENERATOR/AREA DETECTOR FOR STRUCTURAL BIOLOGY

请拨资金用于获取区域探测器数据 用于大分子X射线结晶学的采集系统。这 系统将满足四个结构生物学小组的需求 布兰迪斯罗森斯蒂尔基础医学研究中心 大学。这些团体加起来有近50人携带 生物大分子的OUT衍射研究 从小蛋白质到完整的肌肉纤维。六十多种不同的水晶 系统正在研究中。这些项目的范围从德新星到 晶体结构溶液在突变蛋白研究中的应用 通过定点突变来指导观察 酶-底物及其中间体络合物的低温X射线研究 从结晶学到整个结合表面的作图 有机化合物中晶体大分子的结构测定 溶剂。这些项目对人类的许多领域都具有重要意义 健康。例如，对肌肉蛋白质成分的研究是非常重要的 对了解和治疗神经肌肉疾病的重要性。 结合面的映射对于合理的设计具有重要意义。 毒品。对胰岛素和醛糖还原酶的研究提供了至关重要的 为两种类型设计更有效的治疗方法的信息 I型和II型糖尿病。这些只是几个例子；几乎所有的 这些项目与健康直接相关。所要求的设备是 一种高亮度0.3 mm焦斑的旋转阳极发生器， 一种配备有聚焦镜光学元件的成像板面积探测器， 和低温系统，允许在非常低的温度下收集数据。 这种设备对于许多项目来说是必不可少的，其中 晶体很小和/或晶胞非常大 晶体对辐射敏感。所请求的设备将允许 我们将执行目前不可行的项目 数据收集设施。此外，在某些情况下， 新设备的供应将极大地促进 完成目前进展非常缓慢的项目。

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.