STRUCTURE, FUNCTION & STABILITY OF T4 PHAGE LYSOZYME

爵士提供了(L)-TE-MET；1.8G这一主要目标 建议使用T4溶菌酶作为模型系统，更好地理解 决定折叠、稳定性、结构和性能的因素 蛋白质的功能。要完成的具体研究 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 在残基中，T4溶菌酶对折叠和稳定性至关重要。 我们不仅想了解给定的残基如何有助于 稳定性，以及定义元素的信号(如果有的话) 二级结构。最终，我们希望减少氨基 T4溶菌酶的酸序列到最简单的形式，仍然会给出 一种折叠的有功能的蛋白质。(B)蛋氨酸替代，连同 与其他非极性替代，将被用来更好地理解 对蛋白质折叠至关重要的核心-堆积相互作用。 (C)将开发和测试提高蛋白质稳定性的方法。 (D)T4溶菌酶内的空洞将被利用来理解 蛋白质-配体相互作用和设计新的活性位点。(E) 我们将系统地分析菌株在蛋白质中的作用。

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.