STRUCTURAL STUDIES OF BPTI FOLDING MUTANTS

BPTI 折叠突变体的结构研究

• 批准号: 3468306
• 负责人: TERRENCE GILBERT OAS
• 金额: $ 7.64万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3468306
• 关键词: acidity /alkalinity; biophysics; chemical kinetics; circular dichroism; computer program /software; conformation; intermolecular interaction; model design /development; molecular dynamics; mutant; nuclear magnetic resonance spectroscopy; peptide analog; peptide chemical synthesis; physical model; protein biosynthesis; protein folding; protein purification; protein sequence; protein structure function; site directed mutagenesis; synthetic peptide; thermostability; trypsin inhibitors

The goal of this project is to achieve a better understanding of how protein folding pathways are determined by amino acid sequence. This problem has recently become extremely important in biomedical research because the emergence of techniques for gene-sequencing has produced the sequence of hundreds of proteins whose three-dimensional structure is not known. A more complete understanding of protein folding will improve our ability to predict protein structure from sequence, providing structural insight into the function of the many gene products that play important roles in human disease. The work described in this proposal seeks to explain, in structural terms, the folding kinetics of bovine pancreatic trypsin inhibitor (BPTI). This will be done using a recently developed peptide model of a BPTI folding intermediate called P(alpha)P(beta)2. The native structure and dynamics of several mutants of BPTI that display altered folding kinetics will also be studied. The principle structural method to be employed is two dimensional nuclear magnetic resonance (2D-NMR). This method is capable of providing high resolution structural information for molecules in solution.

本项目的目标是更好地了解如何 蛋白质折叠途径由氨基酸序列决定。这 最近，一个问题在生物医学研究中变得极其重要 因为基因测序技术的出现， 数百种蛋白质的序列，其三维结构不是 知道的对蛋白质折叠的更全面的了解将提高我们的 从序列中预测蛋白质结构的能力，提供结构 深入了解许多重要基因产物的功能 在人类疾病中的作用 本建议中所述的工作试图从结构上解释， 牛胰蛋白酶抑制剂（BPTI）的折叠动力学。这 将使用最近开发的BPTI折叠的肽模型来完成 中间体称为P（alpha）P（beta）2。自然结构和动力学 还将研究几种显示改变的折叠动力学的BPTI突变体。 研究了采用的主要结构方法是二维的 核磁共振（2D-NMR）。该方法能够提供 溶液中分子的高分辨率结构信息。