Slow Protein Dynamics Elicits New Enzymatic Functions by Means of Epistatic Interactions.

ABSTRACT: Protein evolution depends on the adaptation of these molecules to different functional challenges. This occurs by tuning their biochemical, biophysical, and structural traits through the accumulation of mutations. While the role of protein dynamics in biochemistry is well recognized, there are limited examples providing experimental evidence of the optimization of protein dynamics during evolution. Here we report an NMR study of four variants of the CTX-M β-lactamases, in which the interplay of two mutations outside the active site enhances the activity against a cephalosporin substrate, ceftazidime. The crystal structures of these enzymes do not account for this activity enhancement. By using NMR, here we show that the combination of these two mutations increases the backbone dynamics in

SUBMITTER: Rossi MA 

PROVIDER: S-EPMC9547502 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature