Scientists map protein changes to reverse antibiotic resistance in bacteria
Researchers have developed computational tools that pinpoint which parts of resistance-causing proteins can be engineered to restore antibiotic effectiveness. The work offers a blueprint for designing next-generation antibiotics to combat drug-resistant bacteria—a growing threat to hospitals and public health systems worldwide.
Originaltitel: Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN
<p>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 beta-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. We have developed novel tools to characterize evolutionarily conserved non-covalent interactions in proteins. We showcase their application to understanding substrate specificity in class A beta-lactamases, with potential impact for protein engineering.</p>