Studies Toward the Rational Design of Ion Binding Proteins

离子结合蛋白合理设计的研究

• 批准号: 9706904
• 负责人: James Cowan
• 金额: $ 31万
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 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: 1997-07-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9706904&HistoricalAwards=false
• 关键词: Studies; Toward; Rational; Design; Ion

This award in the Inorganic, Bioinorganic and Organometallic Chemistry Program with a contribution from the Mathematics and Physical Sciences Office of Multidisciplinary Activities for instrumentation supports work in the laboratory of Professor James Cowan in the Department of Chemistry at Ohio State University. The research will examine and compare the Mg(II) binding domains of E.Coli RNase H, exonuclease II and other proteins. Since Mg(II) must be recruited from the environment or cellular medium and binding affinities are often not high, the stoichiometry of this metal cofactor required to effect hydrolysis is often not well defined. While the metal binding domains show considerable variation in charge density and coordination for the metal, they have comparable binding affinities. Studies will focus on calorimetric and NMR investigations of Mg binding to native and mutant enzymes. The results will form the basis for the rational design of proteins with novel cation or anion binding chemistry. This research involves a systematic investigation to define the relative importance of Mg(II) inner and outer-sphere coordination, metal ion charge density and solvation, binding affinity and other factors in the use of Mg(II) in important hydrolytic enzymes. Not only should these studies improve our understanding of the role of magnesium in proteins, but results should also prove highly significant in the rational design of ion binding sites in proteins.

该奖项在无机，生物无机和有机 化学计划与数学和物理的贡献 仪器多学科活动科学办公室 支持詹姆斯科万教授实验室的工作， 俄亥俄州州立大学化学系。 这项研究将 检查和比较大肠杆菌RNA酶H的Mg（II）结合结构域， 核酸外切酶II和其他蛋白质。 由于Mg（II）必须从 环境或细胞介质和结合亲和力通常不 高，该金属辅因子的化学计量需要实现 水解作用常常不能很好地定义。 虽然金属结合域 显示出相当大的变化，在电荷密度和协调的 金属，它们具有可比的结合亲和力。 研究将集中在 Mg与天然和突变体结合的量热和NMR研究 内切酶 研究结果将为合理设计 具有新颖的阳离子或阴离子结合化学的蛋白质。 这项研究涉及系统的调查，以确定 Mg（II）内外球配位的相对重要性，金属 离子电荷密度和溶剂化作用、结合亲和力和其它因素 Mg（II）在重要水解酶中的应用。 这些不仅应该 研究提高了我们对镁在蛋白质中的作用的理解， 但结果也应该证明在合理的设计中是非常重要的， 蛋白质中的离子结合位点。