THE PATHWAY TO HEME-IRON LIBERATION IN STAPHYLOCOCCUS AUREUS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 对于细菌病原体来说，人体代表着一个严格限制铁的环境。血红素铁是人体内最普遍的铁源，为了对抗铁的限制，许多细菌病原体已经开发了利用它的系统。成功的革兰氏阳性细菌，金黄色葡萄球菌，利用最近发现的铁调节表面决定簇(ISD)系统从其宿主获得血红素铁。我们最近利用SSRL收集的数据进行的结构研究，确定了血红素与ISD系统关键成分结合的细节。下一步是确定从宿主来源提取亚铁血红素、转移亚铁血红素和胞质亚铁血红素降解的机制。方法是使用X射线结晶学结合定点突变、血红素类似物结合和络合物形成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The human body represents a severely iron-restricted environment for bacterial pathogens. Heme-iron is the most prevalent iron source in the human body and to combat iron-restriction, many bacterial pathogens have developed systems for its utilization. The successful Gram-positive bacterial pathogen, Staphylococcus aureus, employs the recently discovered Iron-regulated surface determinant (Isd) system to acquire heme-iron from its host. Recent structural studies we carried out, using data collected at SSRL, have determined the details of heme binding to key components of the Isd system. The next step is to define the mechanism of heme extraction from host sources, heme transfer, and cytoplasmic heme degradation. The approach is to use x-ray crystallography combined with site directed mutagenesis, heme analog binding and complex formation.