Engineering Fe Site Into Host Proteins

这项由多学科活动办公室资助的无机化学、生物无机化学和金属有机化学项目的奖项支持耶鲁大学约翰·卡拉多纳教授的实验室研究。本研究采用半合成设计方法探讨了蛋白质对铁硫蛋白中铁/S立方的还原电位和电子转移活性以及含铁超氧化物歧化酶中铁位置的影响。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。该超氧化物歧化酶蛋白具有催化活性。这些蛋白质现在将通过一系列物理方法进行表征，以系统地确定氢键、局域电荷和偶极对蛋白质中金属中心电子转移活性的影响。这项研究利用了一项新的成果，通过将铁结合到宿主蛋白质中来研究蛋白质中的金属中心。目的是在已知结构的宿主蛋白内构建具有功能的金属蛋白活性位点。这使得可以高度控制金属中心的环境，这为系统地研究蛋白质对金属中心活性的影响提供了条件。

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.