STRUCTURE DETERMINATION OF HEME OXYGENASE

血红素加氧酶的结构测定

• 批准号: 7955469
• 负责人: KELLIE HOM
• 金额: $ 0.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955469
• 关键词: Area; Bacteria; Bacterial Infections; Binding; Carrier Proteins; Catalysis; Chimera organism; Computer Retrieval of Information on Scientific Projects Database; Computer software; Corynebacterium diphtheriae; DNA Binding; Data; Diphtheria; Enzymes; Funding; Grant; Heme; Hemeproteins; Imagery; Informatics; Institution; Iron; Link; Membrane; Molecular; Neisseria meningitidis; Optics; Oxygenases; Periplasmic Binding Proteins; Proteins; Research; Research Personnel; Resources; Shigella dysenteriae; Site-Directed Mutagenesis; Source; Structure; Techniques; Therapeutic Agents; United States National Institutes of Health; Virulence; X-Ray Crystallography; absorption; biocomputing; design; heme a; interest; pathogen; pathogenic bacteria; receptor; 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. This project focuses on the relationship of structure to function in heme proteins. An area of particular interest is the acquisition and utilization of heme by bacterial pathogens such as Shigella dysenteriae, Neisseriae meningitidis and Corynebacterium diphtheriae. Iron is essential for the survival of all bacteria and many pathogenic bacteria have developed sophisticated mechanisms by which they utilize the hosts heme containing proteins as a source of iron. The ability of pathogenic bacteria to acquire iron is in part linked to their virulence. Understanding the mechanism of heme uptake and iron release at the molecular level will allow rational design of therapeutic agents for the treatment of bacterial infections. The expression and characterization of the outer-membrane receptor (Shu A), periplasmic binding protein (ShuT) and a heme-DNA binding hemeprotein (Shu S) from S. dysenteriae will allow characterization of the the heme transport proteins. In addition the recent expression of heme degrading enzymes from C. diphtheriae (HmuO) and Neisseriae meningitidis (HemO) have allowed the mechanism of iron release to be investigated. Site-directed mutagenesis together with biophysical techniques such as optical absorption, resonance Raman, NMR and X-ray crystallography are used to determine the structural features required for heme binding, transport and catalysis. Software available at CGL, especially Chimera, Midas and Sparky will be used extensively to analyze and view the NMR data and structures of these molecules.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目着重于结构的关系 血红素蛋白。特别感兴趣的领域是通过细菌病原体（例如志贺氏菌，脑膜炎脑膜炎和甲状腺杆菌）的细菌病原体获得和利用。铁对于所有细菌的生存至关重要，许多致病细菌已经开发出复杂的机制，通过这些机制，它们利用含有蛋白质的宿主血红素作为铁的来源。致病细菌获得铁的能力部分与它们的毒力有关。了解在分子水平上血红素摄取和铁释放的机制将使治疗剂的理性设计用于治疗细菌感染。 来自s. dysenteriae的外膜受体（SHU A），周质结合蛋白（SHU A），周质结合蛋白（闭合）和血红素-DNA结合蛋白（SHUS）的表达和表征将允许表征血红素转运蛋白。此外，最近来自白喉（HMUO）和奈瑟氏菌脑膜炎（Hemo）的血红素降解酶（Hemo）的表达允许研究铁释放机理。定点诱变以及生物物理技术（例如光吸收，共振拉曼，NMR和X射线晶体学）用于确定血红素结合，运输和催化所需的结构特征。 CGL上可用的软件，尤其是Chimera，Midas和Sparky，将广泛用于分析和查看这些分子的NMR数据和结构。