ArticleFrontiers in molecular biosciences2020
Known Evolutionary Paths Are Accessible to Engineered ß-Lactamases Having Altered Protein Motions at the Timescale of Catalytic Turnover.
Article in Frontiers in molecular biosciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Dynamic signature of activity-stability tradeoff in lactamase evolution.Nature communications · 2026Article
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
- Tuning Selectivity in CalA Lipase: Beyond Tunnel Engineering.Biochemistry · 2023Article
- Experimental andACS infectious diseases · 2022Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
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Abstract
The evolution of new protein functions is dependent upon inherent biophysical features of proteins. Whereas, it has been shown that changes in protein dynamics can occur in the course of directed molecular evolution trajectories and contribute to new function, it is not known whether varying protein dynamics modify the course of evolution. We investigate this question using three related ß-lactamases displaying dynamics that differ broadly at the slow timescale that corresponds to catalytic turnover yet have similar fast dynamics, thermal stability, catalytic, and substrate recognition profiles. Introduction of substitutions E104K and G238S, that are known to have a synergistic effect on function in the parent ß-lactamase, showed similar increases in catalytic efficiency toward cefotaxime in the related ß-lactamases. Molecular simulations using Protein Energy Landscape Exploration reveal that this results from stabilizing the catalytically-productive conformations, demonstrating the dominance of the synergistic effect of the E014K and G238S substitutions
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