Engineering Fe Site Into Host Proteins

将 Fe 位点改造为宿主蛋白

• 批准号: 9708030
• 负责人: John Caradonna
• 金额: $ 37万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9708030&HistoricalAwards=false
• 关键词: Engineering; Fe; Site; Into; Host

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program with instrumentation funding from the Office of Multidisciplinary Activities supports research in the laboratory of Professor John Caradonna at Yale University. The research involves a semisynthetic design approach to probe the protein effects on the reduction potential and electron transfer activity of the Fe/S cube in iron-sulfur proteins and the iron site in iron-containing superoxide dismutase (SOD). Selectively mutated proteins have already been designed by computer methods and constructed by biological techniques. The SOD protein exhibits catalytic activity. The proteins will now be characterized by an array of physical methods to systematically determine the effects of hydrogen bonding, localized charges and dipoles on the electron transfer activities of the metal centers in the proteins. This research utilizes a new achievement in the study of metal centers in proteins by incorporating iron sites into host proteins. The objective is to construct functional metalloprotein active sites inside host proteins of known structure. This allows a high degree of control of the environment of the metal center, which provdes for systematically studying the effects of the protein on the metal site's activity.

该奖项属于无机、生物无机和有机金属化学项目，由多学科活动办公室提供仪器资助，支持耶鲁大学约翰·卡拉多纳教授实验室的研究。 该研究采用半合成设计方法，探讨蛋白质对铁硫蛋白中 Fe/S 立方体的还原电位和电子转移活性以及含铁超氧化物歧化酶 (SOD) 中铁位点的影响。 选择性突变的蛋白质已经通过计算机方法设计并通过生物技术构建。 SOD 蛋白具有催化活性。 现在将通过一系列物理方法对蛋白质进行表征，以系统地确定氢键、局部电荷和偶极子对蛋白质中金属中心的电子转移活性的影响。 这项研究利用了蛋白质金属中心研究的新成果，将铁位点整合到宿主蛋白质中。 目的是在已知结构的宿主蛋白内构建功能性金属蛋白活性位点。 这使得可以高度控制金属中心的环境，从而可以系统地研究蛋白质对金属位点活性的影响。