Presidential Young Investigator Awards

这项研究的目的是了解氨基酸 酶的序列编码其三维结构， 以及这种结构如何在功能中表现出来。酶 功能和蛋白质结构都是 分子识别 私家侦探使用化学工具， 生物化学和分子生物学来确定分子 识别导致酶的作用。 研究集中在 分子识别的两个方面：酶-底物识别 (that酶催化）和分子内蛋白质-蛋白质 识别（即蛋白质折叠）。 雷恩斯医生正专注于 核糖核酸酶A（RNase A）的催化和折叠。 通过 详细分析了突变型RNase的结构和功能 它们描绘了特定氨基酸的作用 酸残基对底物识别和周转的影响， 蛋白质折叠 他们还对蛋白质二硫化物感兴趣 异构酶（PDI），催化二硫键的交换 其他蛋白质的化学键。 他们克隆了编码 并试图在酵母中表达。 目标是 阐明PDI的催化机理。 相当 正在努力开发有效的、选择性的催化剂 用于合成和降解复杂分子。 多 这一努力的灵感来自于对自然界的研究， 催化剂和酶 阐明了分子间的相互作用 引起底物结合和周转的可能提供 设计蛋白质结构所需的知识， 一种特殊的化学反应。 这些知识，加上 能够指定一个氨基酸序列，折叠成一个 所需的三维结构，将允许蛋白质 工程师们为药物分析创造新的催化剂， 治疗和工业过程。

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.