Phosphate ions modulate enzyme activity and epistatic effects in two clavulanic acid-resistant β-lactamase mutants.

ABSTRACT: Epistasis, the non-additive effect of mutations, substantially undermines our ability to predict the evolutionary trajectories of enzymes. Epistatic effects are evident in the evolution of serine β-lactamases, where synergistic mutations can enhance antimicrobial resistance. We recently demonstrated that positive epistasis drives clavulanic acid resistance in double-mutant libraries of the β-lactamase BlaC. Here, we employed various biochemical and structural approaches to investigate molecular mechanisms underlying epistasis in the fitness of two double mutant variants, I105Y-S130G and I105G-G132N. For the latter enzyme, epistatic compensation of catalytic activity was detected for multiple substrates and proved to be highly buffer-dependent. Non-additive effects were also evident in the

SUBMITTER: Radojkovic M 

PROVIDER: S-EPMC12514841 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature