Upgrade of a Core Laboratory Macromolecular X-ray Diffraction System

项目摘要 这项共享仪器赠款提案的目的是提高大分子X的能力， 德克萨斯大学圣安东尼奥健康科学中心的X射线晶体学（UT Health） 晶体学核心实验室（XRC），位于生物化学与结构生物学系， 乔河和特蕾莎·洛扎诺·朗医学院XRC有20年的历史，是一个机构， 研究中心隶属于研究副总裁办公室，也是药物发现和结构研究中心的一部分。 生物学共享资源下的NCI-designated梅斯癌症中心。它提供结晶，X- 射线衍射数据收集和大分子结构测定服务， 整个机构，其中心和圣安东尼奥地区的项目。仪器的用户包括 癌症生物学、DNA损伤和修复、先天免疫、感染性 疾病和药物设计，仅举几例。 XRC中的当前资源包括MicroMax 007 HF X射线发生器，其驱动两个端口， VariMax-HR和HF共焦光学器件瞄准两个安装的R-AXIS HTC成像板探测器。007HF 旋转阳极发电机忠实地为XRC用户服务，并将在未来几年内提供功能和支持， 来自制造商Rigaku（自1951年以来一直在经营）。然而，成像板检测器已经被 从今年开始，这些产品将不再有资格获得零件支持。既要继续， 为了增强XRC的操作，我们建议用一个HyPix升级/替换两个探测器和光学系统， 6000 HE光子计数探测器安装在通用Kappa测角仪和VariMax VHF共焦 具有连续可调发散狭缝组件的微聚焦光学器件。新仪器将 安装在现有的X射线发生器上，取代两个过时的成像板系统，并将 使用现有的Oxford Cryostream 800冷却系统成像板技术是两代 技术落后，被电荷耦合器件（CCD）探测器和现在的光子计数所取代 探测器HyPix-6000 HE的成像性能明显优于成像板技术，并在CCD上进行了改进 光子计数探测器中技术具有高灵敏度和动态范围，同时消除误差 这是由于读出噪声和暗电流。其他主要优点是速度和数据量， 通过我们成像板上的光子计数探测器获取。HyPix-6000 HE可以获得完整的 在几分钟到几小时的时间尺度中处理数据集，而图像板需要几小时到几天。总体看 要求升级到XRC将有利于调查人员快速，高质量，高分辨率的数据收集 快速完成与人体健康相关的大分子的结构测定。

Project Summary The aim of this Shared Instrumentation Grant proposal is to enhance capabilities for macromolecular X- ray crystallography at the University of Texas Health Science Center at San Antonio (UT Health) X-ray Crystallography Core Laboratory (XRC), located in the Department of Biochemistry & Structural Biology within the Joe R. and Teresa Lozano Long School of Medicine. The XRC has a 20-year history and is an Institutional Research Core under the Office of the Vice President for Research and part of the Drug Discovery & Structural Biology Shared Resource under the NCI-designated Mays Cancer Center. It provides crystallization, X- ray diffraction data collection and macromolecular structure determination services for a wide variety of projects throughout the institution, its centers and the San Antonio area. Users for the instrumentation are investigators for topics such as cancer biology, DNA damage and repair, innate immunity, infectious disease, and drug design to name a few. Current resources in the XRC include a MicroMax 007HF X-ray generator driving two ports with VariMax-HR and HF confocal optics aimed at two mounted R-AXIS HTC imaging plate detectors. The 007HF rotating anode generator has faithfully served XRC users and will be functional and supported for years to come by the manufacturer Rigaku (in business since 1951). However, the imaging plate detectors have been phased out by Rigaku and are no longer eligible for parts support beginning this year. To both continue and enhance XRC operation, we propose to upgrade/replace the two detectors and optics with a single HyPix- 6000HE photon counting detector mounted on a Universal Kappa Goniometer and a VariMax VHF confocal microfocus optic with a continuously adjustable divergence slit assembly. The new instrumentation will be mounted on the existing X-ray generator, taking the place of both obsolete imaging plate systems, and will also use the existing Oxford Cryostream 800 cooling system. The imaging plate technology is two generations behind in technology, superseded by charge coupled device (CCD) detectors and now photon counting detectors. The HyPix-6000HE significantly outperforms imaging plate technology and improves upon CCD technology in that photon counting detectors have high sensitivity and dynamic range while eliminating error due to readout noise and dark current. Additional major advantages are the speed and volume of data that can be acquired by photon counting detectors over our imaging plates. The HyPix-6000HE can acquire full datasets in the timescale of minutes to hours while the image plates require hours to days. Overall, the requested upgrade to the XRC will benefit investigators with rapid, high quality, high resolution data collection to accomplish structure determinations of macromolecules relevant to human health in short order.