STRUCTURE, FUNCTION & STABILITY OF T4 PHAGE LYSOZYME

结构、功能

• 批准号: 6281469
• 负责人: BRIAN W MATTHEWS
• 金额: $ 2.13万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 1999-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281469
• 关键词: bacteria; bioengineering /biomedical engineering; biomedical resource; biotechnology; virus

The SIR provided (l)-te-met; 1.8g The principal objective of this proposal is to use T4 lysozyme as a model system to better understand the factors that determine the folding, stability, structure and function of proteins. The specific research to be accomplished includes the following: (a) An attempt will be made to simplify the protein folding problem by identifying which residues, or combinations of residues, in T4 lysozyme are critical for folding and stability. We want to understand not only how given residues contribute to stability, but also the signals, if any, that define the elements of secondary structure. Ultimately we would like to reduce the amino acid sequence of T4 lysozyme to the simplest form that will still give a folded, functional protein. (b) Methionine substitution, together with other nonpolar replacements, will be used to better understand the core-packing interactions that are critical to protein folding. (c) Methods will be developed and tested to improve protein stability. (d) Cavities within T4 lysozyme will be exploited both to understand protein-ligand interaction and to engineer novel active sites. (e) The role of strain within the protein will be systematically analyzed.

SIR 提供了 (l)-te-met； 1.8g 本文件的主要目标 建议使用T4溶菌酶作为模型系统以更好地理解 决定折叠、稳定性、结构的因素 蛋白质的功能。 需完成的具体研究 包括以下内容： (a) 将尝试简化 通过识别哪些残基或组合来解决蛋白质折叠问题 T4 溶菌酶中的残基对于折叠和稳定性至关重要。 我们不仅想了解给定的残基如何促进 稳定性，以及定义要素的信号（如果有的话） 二级结构。 最终我们希望减少氨基 T4 溶菌酶的酸序列为最简单的形式，仍然给出 一种折叠的功能性蛋白质。 (b) 甲硫氨酸一起取代 与其他非极性替代品，将用于更好地理解 对蛋白质折叠至关重要的核心堆积相互作用。 (c) 将开发和测试方法以提高蛋白质稳定性。 (d) T4 溶菌酶内的空腔将被利用来理解 蛋白质-配体相互作用并设计新的活性位点。 （五） 菌株在蛋白质中的作用将被系统分析。