STRUCTURE/FUNCTION OF SIDEROPHORES

铁载体的结构/功能

• 批准号: 2173801
• 负责人: DICK VAN DER HELM
• 金额: $ 24.56万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2173801
• 关键词: Escherichia coli; Fungi; Mossbauer spectrometry; Pseudomonas; X ray crystallography; active transport; aluminum; bacterial proteins; binding proteins; bioenergetics; biological transport; chemical bond; circular dichroism; conformation; crystallization; gallium; hydroxamate; ion transport; iron metabolism; membrane proteins; metal complex; metalloproteins; microorganism metabolism; nuclear magnetic resonance spectroscopy; protein structure; radiotracer; siderophores; stereoisomer; transport proteins; virulence

Siderophores are secondary metabolites produced by microorganisms to acquire Fe(III) from the aerobic environment. The ferrisiderophores are transported into the cells by an high affinity uptake system which uses several membrane proteins. Many different siderophores are produced for competitive reasons and therefore a variety of matching uptake systems exist. The present research will concentrate on the discovery of new siderophores primarily from pathogenic species and attempt an explanation of the specificity of siderophores for Fe+++, using normal and high-angle x-ray diffraction and other structural techniques. Structural studies will be performed on orally effective synthetic analogs used against iron overload and the stereochemistry of ferrisiderophores will be explored by theoretical methods, modeling and structure determinations. A large quantity of the purified FepA, E. coli receptor protein for Fe(III) enterobactin will be produced and used to improve the quality of FepA crystals and to prepare crystals of heavy atom derivatives to be used in the structure determination of the protein. A concentrated study will be made on the binding properties and other physical-chemical properties of isolated and purified receptor and transport proteins involved in translocation and uptake of ferrisiderophores in E. coli and several Pseudomonas species as well as fungus. These results will be correlated with kinetic transport studies. The research is planned to understand the competitiveness and pathogenicity of microbes in infection and their antagonism in the environment and, most important, to obtain a molecular understanding of transmembrane iron transport.

铁载体是微生物产生的次级代谢产物 从有氧环境中获取Fe（III）。 亚利列载体是 通过使用高亲和力吸收系统运输到细胞中 几种膜蛋白。 为 竞争性原因，因此各种匹配的吸收系统 存在。 本研究将集中于发现新的 铁载体主要来自致病物种，并尝试解释 使用正常和高角度的铁载体对Fe +++的特异性 X射线衍射和其他结构技术。 结构研究将 在针对铁的口服有效的合成类似物上进行 超负荷和运利载体的立体化学将由 理论方法，建模和结构确定。 一个大 Fe（III）的纯化FEPA，大肠杆菌受体蛋白的数量 将生产并用于提高FEPA的质量 晶体并制备用于使用的重原子衍生物的晶体 蛋白质的结构测定。 集中研究将是 在结合特性和其他物理化学特性上 涉及的分离和纯化的受体和转运蛋白 大肠杆菌和几个 假单胞菌和真菌。 这些结果将相关 进行动力学运输研究。 该研究计划了解 微生物在感染中的竞争力和致病性 在环境中的对抗，最重要的是要获得分子 了解跨膜铁运输。