Presidential Young Investigator Awards

本研究的目的是了解酶的氨基酸序列如何编码其三维结构，以及这种结构如何在功能上表现出来。酶的功能和蛋白质的结构都是分子识别的表现。PI正在使用化学，生物化学和分子生物学的工具来确定分子识别如何导致酶的作用。研究集中在分子识别的两个方面：酶-底物识别（即酶催化）和分子内蛋白质-蛋白质识别（即蛋白质折叠）。Reines博士专注于核糖核酸酶A （RNase A）的催化和折叠。通过详细分析突变RNase A的结构和功能，他们描绘了特定氨基酸残基对底物识别和周转以及蛋白质折叠的贡献。他们还对蛋白质二硫异构酶（PDI）感兴趣，它催化其他蛋白质中二硫键的交换。他们已经克隆了编码PDI的cDNA，并试图在酵母中表达。目的是阐明PDI的催化机理。人们正在作出相当大的努力来开发合成和降解复杂分子的高效、选择性催化剂。这项工作的许多灵感来自于对自然界催化剂——酶的研究。阐明导致底物结合和周转的分子相互作用可能为设计催化特定化学反应的蛋白质结构提供必要的知识。这些知识，再加上指定氨基酸序列折叠成所需的三维结构的能力，将使蛋白质工程师能够为药物分析和治疗以及工业过程创造新的催化剂。

The goal of this research is to understand how the amino acid sequence of an enzyme encodes its three-dimensional structure, and how this structure manifests itself in function.Enzyme function and protein structure are both manifestations of molecular recognition. The PI is using the tools of chemistry, biochemistry, and molecular biology to determine how molecular recognition leads to enzyme action. The research concentrates on two facets of molecular recognition: enzyme-substrate recognition (that is, enzymatic catalysis) and intramolecular protein-protein recognition (that is, protein folding). Dr. Reines is focusing on catalysis by and folding of ribonuclease A (RNase A). By analyzing in detail the structure and function of mutant RNase A's, they are delineating the contribution of particular amino acid residues to substrate recognition and turnover and to protein folding. They are also interested in protein disulfide isomerase (PDI), which catalyzes the interchange of disulfide bonds in other proteins. They have cloned the cDNA that codes for PDI, and are attempting to express it in yeast. The goal is to illuminate the mechanism of catalysis by PDI. A considerable effort is being made to develop efficient, selective catalysts for the synthesis and degradation of complex molecules. Much inspiration for this effort has come from the study of nature's catalysts, the enzymes. Illuminating the molecular interactions that give rise to substrate binding and turnover may provide the knowledge necessary to design a protein structure that catalyzes a specific chemical reaction. This knowledge, together with the ability to specify a sequence of amino acids that folds into a desired three-dimensional structure, would allow protein engineers to create novel catalysts for medicinal analyses and therapies, and for industrial processes.