Engineering an Fe SOD Active Site into a Host Protein

将 Fe SOD 活性位点改造为宿主蛋白

• 批准号: 9419178
• 负责人: John Caradonna
• 金额: $ 5万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-15 至 1995-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9419178&HistoricalAwards=false
• 关键词: Engineering; Fe; SOD; Active; Site

This Small Grant for Exploratory Research is supported by the Inogranic, Bioinorganic, and Organometallic Chemistry Program for development of a novel synthetic route to functional metalloproteins. Dr. John Caradonna of the Department of Chemistry, Yale University, will use a combinatorial approach to construct proteins with active metal sites inside host proteins of known structure. Effectively, reaction initiates a search for the constellation of backbone positions that satisfies the geometry of the active site without affecting the host protein's tertiary structure. The mutant proteins constructed would be tested for enzymatic activity. The initial experiments will attempt to synthesize the iron site of superoxide dismutase, so a successful outcome could lead to a powerful tool in reducing tissue damage resulting from superoxide. One immediate result will be the ability to test the effect of secondary protein topologies on the chemistry of metalloproteins. The active sites of metal-containing enzymes consist of metals bound to proteins folded in a certain pattern. By devising a means of adding the metal without disrupting the folding pattern, this research could lead to a method of synthesizing metalloenzymes that are functional, and thus ready for use in biological investigations and applications. In the process, the effect of protein structure on activity of metalloenzymes will be studied.

这项探索性研究的小额资助由Inogranic，Bioinorganic和Organicological Chemistry Program支持，用于开发功能金属蛋白的新型合成途径。 耶鲁大学化学系的John Caradonna博士将使用组合方法构建具有已知结构的宿主蛋白质内的活性金属位点的蛋白质。 有效地，反应开始搜索骨架位置的星座，其满足活性位点的几何形状，而不影响宿主蛋白质的三级结构。 将测试构建的突变蛋白的酶活性。 最初的实验将试图合成超氧化物歧化酶的铁位点，因此成功的结果可能会导致一个强大的工具，减少超氧化物引起的组织损伤。 一个直接的结果将是能够测试二级蛋白质拓扑结构对金属蛋白质化学性质的影响。 含金属酶的活性部位由与蛋白质结合的金属组成，这些金属以一定的模式折叠。 通过设计一种在不破坏折叠模式的情况下添加金属的方法，这项研究可能会导致一种合成功能性金属酶的方法，从而为生物学研究和应用做好准备。 在此过程中，将研究蛋白质结构对金属酶活性的影响。