COORDIANTION CHEMISTRY OF MICROBIAL IRON TRANSPORT

微生物铁运输的配位化学

• 批准号: 2671669
• 负责人: KENNETH N RAYMOND
• 金额: $ 20.85万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-04-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2671669
• 关键词: chemical binding; chemical kinetics; iron; iron metabolism; nuclear magnetic resonance spectroscopy; protein structure function; siderophores; thermodynamics

DESCRIPTION: Iron is an essential growth element, but the availability of iron in an oxidizing environment is severely limited by the insolubility of Fe(OH)3. Microbes respond to this limitation by synthesizing low-molecular-weight chelating agents, siderophores, for which there are membrane-bound receptors. Often bacteria synthesize several siderophores and/or express multiple receptors. There is a clear link between iron and microbial virulence. Pathogenicity increases of up to 107 have been observed when the bacteriostatic effects of human iron complexing proteins are overcome. Previous studies have focussed on the structures of siderophores and the relationship of stereochemistry to siderophore mediated iron transport. Future work will address the dynamics of siderophore complexation in addition to the identification of new siderophores and their structure/function relationships. Fluorescent probes will be attached to siderophores to monitor both the spatial and temporal uptake of iron mediated by siderophores. The kinetics of ligand exchange and complex isomerization in catechol siderophores will be studied by NMR, and competition experiments will be used to obtain full thermodynamic characterization of siderophores. The overall focus of this research continues to be the coordination chemistry of siderophores, the connection of this chemistry to their biological activity, and the consequent medical significance of the results.

描述：铁是一种重要的生长元素， 铁在氧化环境中的含量受到严格限制， Fe（OH）3的不溶性。 微生物对这种限制的反应是 合成低分子量螯合剂，铁载体， 有膜结合受体。 通常细菌会合成 几种铁载体和/或表达多种受体。 有一个 铁和微生物毒力之间的明确联系。 致病性增加 当人体的抑菌作用时， 铁络合蛋白被克服。 以前的研究集中在 铁载体的结构以及 铁载体介导的铁转运。 未来的工作将 解决铁载体络合的动力学，除了 新铁载体鉴定及其结构/功能 关系。 荧光探针将附着在铁载体上， 监测铁介导的空间和时间摄取， 铁载体 配体交换和配合物异构化动力学 在儿茶酚铁载体将研究核磁共振，和竞争 实验将用于获得完整的热力学特性 铁载体 这项研究的总体重点仍然是 铁载体的配位化学，这种化学的联系 它们的生物活性以及随之而来的医学意义 的结果。