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 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.
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