X-Ray Crystallography

X射线结晶学共享设施的目标是为CCC成员提供支持，以研究 蛋白质的精细结构细节，以及蛋白质结构的功能后果。该设施 通过提供对关键生物物理设施的访问来实现这一点，包括：1)X射线晶体数据 收集(通过内部X射线系统和通过成员资格专用访问两条同步加速器光束线 在Argonne Synchrotron设施的东南协作访问团队(SERCAT)中；2)高吞吐量 水和膜蛋白的纳米结晶；3)一种新技术(由 共享设备总监)可快速优化蛋白质的溶解度和稳定性；4)Biacore；5)高通量 差示扫描量热法和等温量热法；6)圆二色谱(CD)。在过去 在资助期间，该设施支持了40名CCC成员的基础研究和翻译研究，结果 在40多个蛋白质的三维结构中，有12个是癌症治疗的靶点。这些 研究人员在顶级同行评议期刊上发表了96篇研究论文。CCC成员使用 在过去的五年中，共享设施与四个CCC计划有关：癌症化学预防， 病毒学、实验治疗学和癌细胞生物学。这个共享的增值的一个例子 该设备涉及维甲酸X受体RXR的X射线结构，RXR是一种与乳腺癌有关的蛋白质。这个 RXR的高分辨蛋白质结构和复杂结构与14种不同的抑制剂直接结合 支持乳房孢子计划拨款。这项工作帮助开发了一种铅抑制剂(UAB30) RXR，目前处于第一阶段人体临床试验，并继续支持第二代 抑制剂。X射线结晶学共享设施的具体目标包括：a)继续 升级现有技术以维护最先进的设施，并继续采用新颖的 支持结构和生物物理蛋白质表征的技术，b)提供癌症中心 成员经济高效地获得几种不同的生物物理表征技术，以增强 基础和/或转化性癌症研究，c)提供最先进的培训设施，以支持下一步 一代癌症研究科学家，包括研究生和博士后研究员以及 CCC教员，d)继续提供试点/种子补助金(通过其他非CCC可自由支配基金)，以 鼓励新的癌症相关研究。项目通过竞争性的NIH风格的同行审查获得资金 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.