Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN

Abstract

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.

Graphical abstract: Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN

  • This article is part of the themed collection: Biocatalysis

Article information

Article type
Paper
Submitted
02 Feb 2024
Accepted
28 Feb 2024
First published
29 Feb 2024
This article is Open Access
Creative Commons BY license

Faraday Discuss., 2024, Advance Article

Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN

D. Yehorova, R. M. Crean, P. M. Kasson and S. C. L. Kamerlin, Faraday Discuss., 2024, Advance Article , DOI: 10.1039/D4FD00018H

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