X-Ray Crystallography

X射线晶体学共享设施的目标是为CCC成员提供研究支持， 蛋白质的精细结构细节和蛋白质结构的功能后果。该设施 通过提供关键的生物物理设施来实现这一目标，包括：1）X射线晶体学数据 收集（通过内部X射线系统和通过会员资格专用访问两条同步加速器光束线 在阿贡同步加速器设施的东南协作访问小组（SERCAT）中; 2）高通量 水和膜蛋白的纳米结晶; 3）一种新的技术（由 共享设施主任），快速优化蛋白质溶解度和稳定性; 4）BIAcore; 5）高通量 差示扫描量热法和等温量热法;和6）圆二色性（CD）。在过去 在资助期间，该基金支持了40个CCC成员的基础和转化研究， 超过40种蛋白质的三维结构，其中12种是癌症治疗靶点。这些 研究人员在顶级同行评审期刊上发表了96篇研究文章。CCC成员使用 在过去五年中，共享设施与四个CCC项目有关：癌症化学预防， 病毒学、实验治疗学和癌细胞生物学。这个共享的增值的例子 该设备涉及维甲酸X受体的X射线结构，RXR，一种与乳腺癌有关的蛋白质。的 高分辨率蛋白质结构加上RXR直接结合14种不同抑制剂的复杂结构 支持Breast SPORE计划拨款。这项工作有助于开发铅抑制剂（UAB 30）， RXR目前处于I期人体临床试验阶段，并将继续支持第二代 抑制剂的X射线晶体学共享设施的具体目标包括： 升级现有技术，以保持最先进的设施，并继续将新的 支持结构和生物物理蛋白质表征的技术，B）提供癌症中心 成员具有成本效益地获得几种不同的生物物理表征技术， 基础和/或转化癌症研究，c）提供最先进的培训设施，以支持下一个 一代癌症研究科学家，包括研究生和博士后研究员，以及 CCC教职员工，d）继续提供试点/种子补助金（通过其他非CCC自由裁量基金）， 刺激新的癌症相关研究。项目通过竞争性NIH风格的同行评审资助， 提案

The goal of the X-ray Crystallography Shared Facility is to provide CCC members support for research into the fine structural details of proteins, and the functional consequences of protein structures. The facility accomplishes this by providing access to critical biophysical facilities including; 1) X-ray crystallographic data collection (via in-house X-ray systems and dedicated access to two synchrotron beamlines via membership in the Southeastern Collaborative Access Team (SERCAT) at Argonne Synchrotron Facility; 2) highthroughput nano-crystallization for aqueous and membrane proteins; 3) a novel technology (developed by the Shared Facility Director) that rapidly optimizes protein solubility and stability; 4)BIAcore; 5) high-throughput differential scanning and isothermal calorimetry; and 6) circular dichroism (CD). During the past funding period, the facility supported fundamental and translational research by40 CCC members, resulting in over 40 three-dimensional structures for proteins, 12 of which are cancer therapeutic targets. These investigators published 96 research articles in top peer-reviewed journals. CCC members who used the shared facility in the past five years are associated with four CCC programs: Cancer Chemoprevention, Virology, Experimental Therapeutics and Cancer Cell Biology. An example of the value added of this shared facility involves the X-ray structure of the retinoid X receptor, RXR, a protein implicated in breast cancer. The high-resolution protein structure plus complex structures of RXR bound to 14 different inhibitors directly supported the Breast SPORE program grant. This work aided the development of a lead inhibitor (UAB30) of RXR, currently in phase I human clinical trials and is continuing to support the development of second-generation inhibitors. Specific aims of the X-ray Crystallography Shared Facility include: a) Continue to upgrade existing technologies to maintain a state-of-the-art facility and continue to incorporate novel technologies that support structural and biophysical protein characterization, b) Provide Cancer Center members with cost-effective access to several different biophysical characterization techniques to enhance basic and/or translational cancer research, c) Provide a state-of-the-art training facility to support the next generation of cancer research scientists, including graduate students and post-doctoral fellows as well as CCC faculty members, d) Continue to provide pilot/seed grants (via other non-CCC discretionary funds) to stimulate new cancer-related research. Projects are funded through competitive NIH-style peer review of proposals.