Acquisition of a Bruker X8 Prospector Protein X-ray Crystallography System

描述（由申请人提供）：本提案要求提供资金，用于购买新的X射线数据收集系统，作为加州大学欧文分校大分子晶体学的主要数据收集仪器。目前的系统已经使用了11年，每年的维护费用很高。尽管UCI社区广泛使用同步加速器数据收集，但仍然需要一个可靠的内部系统来在同步加速器行程之前筛选晶体，搜索重原子衍生物，并在某些情况下使用内部数据解决结构问题。我们的目标是用一个运行成本低、高度可靠的系统取代旧系统。我们建议购买一个布鲁克X8 Prospector CCD系统，该系统配备Incoatec微焦点密封、空气冷却X射线管和2D Montel多层镜。由于该系统使用密封管，X射线源与旋转阳极相比基本上无需维护。我们预计每年的运营成本将从每年约30，000美元降至每年约5，000美元。有5个主要用户（Goulding，麦克弗森，Tsai，Poulos和Sevrioukova），其中4个由NIH赠款。古尔丁博士在UCI工作了一年，将申请NIH的支持。自1992年Poulos教授被招募到UCI开始在UCI发展结构生物学以来，结构生物学已经大大扩展。现在有6名教师晶体学家，2名NMR光谱学家和3名计算结构生物学家，今年夏天还有两名加入UCI。鉴于晶体学软件、数据收集和结晶已经变得更加用户友好，晶体学项目的范围也扩展到许多其他非正式的晶体学实验室。数十种蛋白质、酶、病毒和抗体结构已被解决，其结果导致了新的分子设计和合成以及动物模型试验。因此，虽然该提案有5个主要用户，但还有6个其他教师实验室也使用当前系统，其中许多是由NIH赠款的。所要求的设备将为NIH资助的10个项目提供主要的现场数据收集系统。公共卫生相关性：在主要用户的实验室中研究的重要健康相关蛋白质的晶体结构为理解功能提供了必要的信息。病毒基因组的结构组织（麦克弗森）、抗生素生物合成的结构生物学（Tsai）、结核病药物靶点的结构生物学（Goulding）、基于结构的一氧化氮合酶抑制（Poulos）和细胞凋亡机制（Sevrioukova）都具有明确定义的健康相关意义。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.