Dariia Yehorova, Rory M. Crean, Peter M. Kasson and Shina Caroline Lynn Kamerlin
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引用次数: 0
摘要
非共价相互作用网络是表示和分析蛋白质结构的有力手段。这种网络既可以表示静态结构,也可以表示动态构象组合。我们最近开发了两种工具,用于分析这种相互作用网络并为蛋白质工程学提出假设。在这里,我们将这些工具应用于 A 类 β-内酰胺酶底物特异性的构象调控,特别是从通用催化功能到专一催化功能的进化发展,以及如何通过蛋白质工程来重现或逆转这种发展。这些工具(KIF 和 KIN)可生成一组优先残基和相互作用,作为蛋白质工程实验的目标。
Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN
Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specificity in class A β-lactamases, particularly the evolutionary development from generalist to specialist catalytic function and how that can be recapitulated or reversed by protein engineering. These tools, KIF and KIN, generate a set of prioritized residues and interactions as targets for experimental protein engineering.