Skip to Main content Skip to Navigation
New interface
Journal articles

The Structural Dynamics of Engineered β-Lactamases Vary Broadly on Three Timescales yet Sustain Native Function

Abstract : Understanding the principles of protein dynamics will help guide engineering of protein function: altering protein motions may be a barrier to success or may be an enabling tool for protein engineering. The impact of dynamics on protein function is typically reported over a fraction of the full scope of motional timescales. If motional patterns vary significantly at different timescales, then only by monitoring motions broadly will we understand the impact of protein dynamics on engineering functional proteins. Using an integrative approach combining experimental and in silico methodologies, we elucidate protein dynamics over the entire span of fast to slow timescales (ps to ms) for a laboratory-engineered system composed of five interrelated β-lactamases: two natural homologs and three laboratory-recombined variants. Fast (ps-ns) and intermediate (ns-µs) dynamics were mostly conserved. However, slow motions (µs-ms) were few and conserved in the natural homologs yet were numerous and widely dispersed in their recombinants. Nonetheless, modified slow dynamics were functionally tolerated. Crystallographic B-factors from high-resolution X-ray structures were partly predictive of the conserved motions but not of the new slow motions captured in our solution studies. Our inspection of protein dynamics over a continuous range of timescales vividly illustrates the complexity of dynamic impacts of protein engineering as well as the functional tolerance of an engineered enzyme system to new slow motions.
Complete list of metadata

Cited literature [73 references]  Display  Hide  Download
Contributor : Michel Courcelles Connect in order to contact the contributor
Submitted on : Friday, August 30, 2019 - 4:16:17 PM
Last modification on : Thursday, September 2, 2021 - 8:14:03 AM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




Sophie Gobeil, Maximillian Ebert, Jaeok Park, Donald Gagné, Nicolas Doucet, et al.. The Structural Dynamics of Engineered β-Lactamases Vary Broadly on Three Timescales yet Sustain Native Function. Scientific Reports, 2019, 9 (1), pp.6656. ⟨10.1038/s41598-019-42866-8⟩. ⟨pasteur-02275345⟩



Record views


Files downloads