STRUCTURE DETERMINATION OF ANTHROLYSIN O, CYTOLYSIN SECRETED BY ANTHRAX BACTERIA

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。 炭疽杆菌是一种具有溶血活性的54 kDa胆固醇依赖型细胞溶血素，它能分泌出具有溶血活性的色素。ALO可在细胞膜上形成低聚孔，破坏细胞内稳态和细胞信号转导。最近我们的实验室发现Alo可以降低极化的肠道上皮细胞的完整性，这可能在胃肠道炭疽感染中起着至关重要的作用。我们已经结晶了AlO，这些晶体的衍射率为3.75°。我们能够用分子置换以非常低的分辨率解决这个结构。我们建议优化结晶条件，以获得衍射到高分辨率的晶体。这项实验的成功将为设计有助于治疗炭疽感染的AlO抑制剂提供蓝图。

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. Anthrax bacteria (Bacillus anthracis) secrete anthrolysin O (ALO), which is a 54 kDa cholesterol dependent cytolysin (CDC) and exhibits hemolytic activity. ALO can form the oligomeric pores in cellular membranes, which can disrupt cell homeostasis and cell signaling. Recently our laboratory has shown that ALO can decrease the integrity of polarized gut epithelial cells, which may play a crucial role for gastrointestinal anthrax infection. We have already crystallized ALO and those crystals diffracted to 3.75 ¿. We were able to solve this structure at a very low resolution using molecular replacement. We propose to optimize the crystallization conditions to yield crystals that diffract to a high resolution. Success in this experiment will provide a blueprint for designing inhibitors of ALO that could aid in the treatment of anthrax infection.