Acquisition of an X-Ray Area Detector

需要一种区域敏感的X射线探测器系统，用于高分辨率蛋白质结构分析的X射线晶体学数据收集。新仪器是为了增强UCSF的结构能力，目前这一能力已被大量超额认购。目前，人们通常轮流等待一个月至六个星期才能使用现有的两个区域探测器中的一个。所要求的新仪器就是要克服结构科学中这一限制速率的步骤。所提出的探测器系统采用了新的荧光粉存储技术，使数据采集更加高效和准确。由于结构分析使我们能够使用许多突变来提出科学问题，或者使用改良的抑制剂来设计改进的治疗方法，单个蛋白质系统的研究可以在一个数据收集仪器上占用多达50%的时间。了解突变蛋白或改变的抑制化合物的特性将需要对结构进行彻底的分析，就像对天然蛋白一样。定点诱变的速度要求快速的结构分析，使科学家能够接近重要的科学问题。在下面的叙述中，我们列出了三位主要研究人员的项目，并说明了对新的公共设备的需求。容纳新机器的实验室将进行翻新：将增加一堵墙，更换管道，安装电气设备，并建造一个安全围栏。这些项目大部分是由NIH资助给三个p.i.的，以叙述的形式简要描述，尽可能引用已发表的作品，然后是一个表格。它按标题列出了各个项目，从事该项目的主要科学家和项目的状态。该状态提供了当前数据收集需求的简要摘要。

ABSTRACT Acquisition of an X-ray Area Detector P.l. Robert J. Fletterick An area sensitive X-ray detector system is requested for X- ray crystallographic data collection for high resolution structure analyses of proteins. The new instrument is to augment the UCSF structural capability which is currently vastly oversubscribed. At present, persons typically wait in turn for one month to six weeks for time on one of the two existing area detectors. The new instrument requested is to overcome this rate limiting step in the structural science. The new phosphor storage technology used in the proposed detector system makes data collection more efficient and accurate. As structural analysis moves us to ask scientific questions using many mutations, or using modified inhibitors aimed at designing improved therapeutics, study of a single protein system can occupy as much as 50% of the time on one data collection instrument. Understanding the properties of mutant proteins or altered inhibitory compounds will require an analysis of structure as thoroughly as for the native proteins. The speed with which site-directed mutagenesis is accomplished requires rapid structural analysis for the scientist to remain close to the important scientific questions. In the following narrative, we list the projects of the three principal investigators and demonstrate the need for the new communal equipment. The laboratory to house the new machines will be renovated: a wall is to be added, plumbing changed, electrical installation and a safety enclosure will be built. The projects, most supported by NIH grants to the three P.I.s, are briefly described in narrative form, with references to published work where possible, and followed by a table. This lists the individual projects by title, the principal scientists working on the project and the status of the project. The status provides a brief summary of the current needs for data collection.