CRYSTAL STRUCTURES OF VIRULENCE FACTORS, HOST MOLECULES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去的5年里，SSRL一直是我的实验室收集x射线数据和分阶段的主要资源。通过在Se， Br和Zn边缘使用MAD相位，我们从头开始确定了许多蛋白质结构。单色x射线的高亮度，准直性和稳定性也使我们能够从具有大单位细胞的晶体中收集高分辨率数据，这为在原子水平上理解生物功能或为药物设计的小分子抑制剂的合理设计提供了必要的数据。我们建议在三个方面继续我们的工作：研究炭疽毒素成分，它们与小分子药物先导物和宿主细胞靶蛋白的复合物；整合素介导细胞迁移的关键结构和信号分子研究以及参与细胞凋亡的分子，包括宿主细胞调节因子和它们的致病颠覆者（毒力因子）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SSRL has been a principal resource for x-ray data collection and phasing for my laboratory over the past 5 years. Through the use of MAD phasing at Se, Br, and Zn edges, we have determined many protein structures ab initio. The high brightness, collimation and stability of the monochromatic x-rays has also allowed us to collect high resolution data from crystals with large unit cells which has provided the necessary data for understanding biological function at the atomic level, or for the rational design of small molecule inhibitors for drug design. We propose to continue our work in three areas: studies of the anthrax toxin components, their complexes with small molecule drug leads and host cell target proteins; studies of key structural and signaling molecules involved in integrin-mediated cell migration; and molecules involved in apoptosis, both host cell regulators and their pathogenic subverters (virulence factors).