BACTERIAL PROTEINS CONTAINING NOVEL IRON SITES

含有新铁位点的细菌蛋白

• 批准号: 2900687
• 负责人: DONALD M. KURTZ
• 金额: $ 15.91万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900687
• 关键词: Desulfovibrio; X ray crystallography; bacterial proteins; enzyme activity; hemerythrin; iron; metalloproteins; oxidation reduction reaction; protein engineering; protein structure function; site directed mutagenesis; spectrometry; structural biology

The overall goal of this project is to understand the structure and function of diiron-oxo sites in proteins. Two such proteins have been chosen as the focus of investigations: hemerythrin (and myohemerythrin), an O 2-carrying protein from marine invertebrates, rubreythrin, a protein of unknown biological function form anaerobic sulfate-reducing bacteria, and bacterioferritin,and iron storage protein found in several bacteria. Since the structure and function of hemerythrin is already known in some detail, the proposed research aims to examine a relatively neglected but crucial aspect, namely, the roles of conserved residues lining the O2 binding pocket in modulation of O2 affinity and in protection of the diiron site against autoxidation. Rubrerythrin is a diiron-oxo from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris. The major unsolved problem for this protein is biological function. The results obtained during the previous projects period show that the diiron domain of the rubreythrin subunit a strong structural resemblance to the subunits of the iron storage proteins, ferritin and bacterioferritin. The results strongly suggest that rubreythrin's biological function involves iron metabolism, perhaps connected to oxygen tolerance of the bacteria. A systematic investigation of the function of rubrerythrin both in vitro and in vivo is proposed. Since many infections bacteria have developed mechanisms for obtaining iron from their host, an understanding of iron metabolism in the bacteria mentioned above will increase our understanding of pathogenesis. This includes anaerobic sulfate-reducing bacteria, which have been found in the human gut. A health-related goal of understanding the dioxygen- carrying mechanism of hemerythrin is to develop this protein for use in blood substitutes.

该项目的总体目标是了解结构和 蛋白质中二氧氧化物位点的功能。两个这样的蛋白质已经 被选为调查的焦点：赫尔梅特林（和myohemerythrin）， 来自海洋无脊椎动物的O 2携带蛋白，Rubreythrin，一种蛋白质 未知的生物学功能形成厌氧性硫酸盐的细菌， 在几种细菌中发现的细菌铁蛋白和铁储存蛋白。 由于某些人已经知道了hemerythrin的结构和功能 细节，拟议的研究旨在检查一个相对忽视但 至关重要的方面，即O2内衬里的保守残基的作用 在调制O2亲和力和保护方面的绑定口袋 二龙网站反对自氧化。 RubreryThrin是来自 厌氧性硫酸盐还原细菌，Deulfovibrio dulgaris。 专业 该蛋白质的未解决问题是生物学功能。 结果 在上一个项目期间获得的表明Diiron域 红宝石亚基与 铁储存蛋白，铁蛋白和细菌铁蛋白的亚基。 结果强烈表明Rubreythrin的生物功能 涉及铁代谢，也许与氧气耐受有关 细菌。 对RubreryThrin的功能的系统研究 提出了体外和体内的。 由于许多感染细菌已经开发了获得的机制 从宿主那里铁，对细菌中铁代谢的理解 上面提到的将增加我们对发病机理的理解。 这 包括在 人类的肠道。 与健康相关的目标，是了解二氧化物 - hele氏蛋白酶的携带机制是开发这种蛋白质供 血液替代品。