ArticleScientific reports2019
The Structural Dynamics of Engineered β-Lactamases Vary Broadly on Three Timescales yet Sustain Native Function.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Dynamic signature of activity-stability tradeoff in lactamase evolution.Nature communications · 2026Article
- Interpretable machine learning classifies β-lactamase subclasses and prioritizes boundary variants for antimicrobial resistance surveillance.Frontiers in pharmacology · 2026Article
- Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Conformational exchange divergence along the evolutionary pathway of eosinophil-associated ribonucleases.Structure (London, England : 1993) · 2023Article
- Slow Protein Dynamics Elicits New Enzymatic Functions by Means of Epistatic Interactions.Molecular biology and evolution · 2022Article
- Editorial: Molecular evolution: You learn from your mistakes.Frontiers in molecular biosciences · 2022Article
- Two β-Lactamase Variants with Reduced Clavulanic Acid Inhibition Display Different Millisecond Dynamics.Antimicrobial agents and chemotherapy · 2021Article
- Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics.eLife · 2021Article
- The Role of Rigid Residues in Modulating TEM-1 β-Lactamase Function and Thermostability.International journal of molecular sciences · 2021Article
- Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics.Nature communications · 2021Article
- The Role of Hydrophobic Nodes in the Dynamics of Class A β-Lactamases.Frontiers in microbiology · 2021Article
- Conformational Dynamics Contribute to Substrate Selectivity and Catalysis in Human Kynureninase.ACS chemical biology · 2020Article
- A mechanistic view of enzyme evolution.Protein science : a publication of the Protein Society · 2020Review
- Allostery and Epistasis: Emergent Properties of Anisotropic Networks.Entropy (Basel, Switzerland) · 2020Article
- Known Evolutionary Paths Are Accessible to Engineered ß-Lactamases Having Altered Protein Motions at the Timescale of Catalytic Turnover.Frontiers in molecular biosciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.