NMR Studies of Enzyme Conformations

本项目的主要目标是评估葡萄球菌核酸酶（Snase）活性位点引入点突变后产生NMR谱变化的构象变化的幅度、位置和意义。该研究将允许研究单位点氨基酸变化如何影响抑制剂-酶相互作用以及蛋白质的构象，以及氨基酸替代引起的构象变化如何与酶活性的变化相关。此外，将继续努力发展新的核磁共振实验，以更可靠地探测感兴趣的相互作用，并发展计算机辅助手段来分析核磁共振数据。与酶活性位点结合的分子构象对于决定酶如何催化反应具有重要意义，它们之间的相互作用对于确定酶的特异性和设计新的酶抑制剂具有重要意义。这个项目是卫斯理化学系唯一一个涉及诱变问题以及蛋白质结构和功能测定的项目。这使本科生能够参与广泛而可行的研究工作。

The primary goal of this project is the assessment of the magnitude, location and significance of the conformational changes that produce NMR spectral changes upon introduction of point mutations in the active site of Staphylococcal nuclease (Snase). The study will allow investigation of how single site amino acid changes affect the inhibitor-enzyme interaction as well as the conformation of the protein and how the conformational changes induced by amino acid replacement are related to changes in enzyme activity. In addition, there will be continued efforts on the development of novel NMR experiments to probe with more reliability the interactions of interest and on the development of computer aided means of analysing NMR data. The conformation of molecules bound to the active sites of enzymes is of importance in determining how enzymes catalyze reactions, which interactions are important in determining enzyme specificity and in the design of new inhibitors of enzymes. This program is the only one in the Wesleyan Chemistry Department concerned with questions of mutagenesis as well as with determinations of protein structure and function. This allows undergraduate students to partake in a broad and viable research effort.