CRYSTALLOGRAPHIC STUDIES OF VIRULENCE FACTORS, HOST-PATHOGEN INTERACTIONS, AND O

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是利丁顿实验室的一个持续提案，描述了我们在SSRL结构生物学方面的整体计划。主要焦点是炭疽毒素和来自其他高优先级病原体和新出现的疾病的毒力因子，以及它们与宿主因子的相互作用，以及参与细胞迁移和炎症的宿主蛋白。这项工作包括通过MAD分期确定从头算结构，用于合理药物设计的蛋白质抑制物复合体的研究，以及用于设计免疫疗法的中和抗体复合体的研究。我报告我们2005-2008年期间的研究重点，结合我们在SSRL的早期工作，以及我们正在进行的和未来的研究。这项工作说明了SSRL是如何在我们科学的大多数方面发挥核心和关键作用的？利用其可调谐性确定一级结构/定相；和/或SSRL源的高亮度、准直性和稳定性，用于从要求苛刻的晶体收集高分辨率数据。而所有这一切都是通过杰出的用户支持小组的奉献而实现的，而且更加令人愉快。

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. This is a continuing proposal for the Liddington laboratory, describing our overall program in structural biology at the SSRL. The major focuses are anthrax toxin and virulence factors from other high priority pathogens and emerging diseases, and their interactions with host factors, as well as host proteins involved in cell migration and inflammation. The work involves ab initio structure determination by MAD phasing, studies of protein-inhibitor complexes for rational drug design, and complexes with neutralizing antibodies for designing immune therapeutics. I report highlights of our studies for the 2005-2008 period in the context of our earlier work at SSRL, as well as our ongoing and future studies. This work illustrates how the SSRL has played a central and critical role in most aspects of our science ? using its tunability for primary structure determination/phasing; and/or the high brightness, collimation and stability of the SSRL source for the collection of high resolution data from demanding crystals. And all of this made possible and much more pleasant through the dedication of the outstanding User Support Group.