STUDIES OF MOLECULAR STRUCTURES OF HEME BINDING PROTEINS FROM PATHOGENIC BACTERI

病原菌血红素结合蛋白分子结构的研究

• 批准号: 7598218
• 负责人: MICHAEL MURPHY
• 金额: $ 0.16万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598218
• 关键词: Affinity; Bacteria; Binding; Campylobacter; Campylobacter jejuni; Computer Retrieval of Information on Scientific Projects Database; Data; Dimerization; Funding; Grant; Heme; Institution; Invaded; Iron; Modeling; Molecular; Molecular Structure; Protein Family; Proteins; Research; Research Personnel; Resolution; Resources; Role; Source; Staphylococcus aureus; Structure; Surface; System; United States National Institutes of Health; base; heme a; heme-binding protein; mutant; novel; pathogen; prevent; uptake

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. Heme is the greatest source of essential iron for pathogens residing within a host. However, the iron is sequestered by the host to prevent its misuse by invading bacteria. Therefore, pathogens have evolved high affinity uptake systems that can specifically recognize and take up host heme. The Isd (iron surface determinant) family of proteins from Staphylococcus aureus and the Cha (Campylobacter heme acquisition) proteins from Campylobacter jejuni are components of characterized heme transport systems. The structural basis for understanding the molecular mechanism of these transport systems is still lacking. Data collected recently on ChaN at the SSRL has been used to determine the structure of the heme-bound protein, which demonstrates a novel model of heme dependent dimerization. Crystal structures of mutants of ChaN will be determined to probe the role of specific residues in heme-dependent dimerization and in interaction with other Cha transport components. Preliminary crystals of a heme binding domains of Isd proteins have been produced and will be optimized for high-resolution structure determination.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 血红素是宿主体内病原体必需铁的最大来源。然而，铁被宿主隔离，以防止其被入侵的细菌滥用。因此，病原体已经进化出高亲和力摄取系统，可以特异性地识别和摄取宿主血红素。来自金黄色葡萄球菌的Isd（铁表面决定簇）蛋白家族和来自空肠弯曲杆菌的Cha（弯曲杆菌血红素获取）蛋白是表征血红素转运系统的组分。理解这些运输系统的分子机制的结构基础仍然缺乏。最近在SSRL上收集的关于ChaN的数据已被用于确定血红素结合蛋白的结构，这证明了血红素依赖性二聚化的新模型。Cha N突变体的晶体结构将被确定，以探测特定残基在血红素依赖性二聚化和与其他Cha转运组分相互作用中的作用。初步晶体的血红素结合结构域的ISD蛋白已经产生，并将优化高分辨率的结构测定。