ArticleNature communications2021
Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
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- Statistical Physics-Based Approaches to Model the Function and Complexation of Disordered Proteins.The journal of physical chemistry. B · 2025Article
- Mutations in active surface sites of NtGGPPS1 enhance carotenoid biosynthesis and drought resistance in Nicotiana tabacum.BMC plant biology · 2025Article
- Second-order allosteric control as a mechanism for compensatory mutations in B-cell translocation gene 2.Protein science : a publication of the Protein Society · 2025Article
- Biosynthetic Pathways of Alaremycin and Its Derivative: Inhibitors of Porphobilinogen Synthase in Porphyrin Biosynthesis fromACS bio & med chem Au · 2025Article
- How enzyme functions evolve: genetic, structural, and kinetic perspectives.Biophysical reviews · 2025Review
- Tailoring industrial enzymes for thermostability and activity evolution by the machine learning-based iCASE strategy.Nature communications · 2025Article
- Global hinge sites of proteins as target sites for drug binding.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Transition Path Sampling Based Free Energy Calculations of Evolution's Effect on Rates in β-Lactamase: The Contributions of Rapid Protein Dynamics to Rate.The journal of physical chemistry. B · 2024Article
- Dynamics-based protein network features accurately discriminate neutral and rheostat positions.Biophysical journal · 2024Article
- The Evolution of the Acylation Mechanism inACS catalysis · 2024Article
- Friends and relatives: insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN.Faraday discussions · 2024Article
- Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science advances · 2024Article
- Simultaneous enhancement of multiple functional properties using evolution-informed protein design.Nature communications · 2024Article
- Article
- Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023Article
- Allosteric regulatory control in dihydrofolate reductase is revealed by dynamic asymmetry.Protein science : a publication of the Protein Society · 2023Article
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
TEM-1 β-lactamase degrades β-lactam antibiotics with a strong preference for penicillins. Sequence reconstruction studies indicate that it evolved from ancestral enzymes that degraded a variety of β-lactam antibiotics with moderate efficiency. This generalist to specialist conversion involved more than 100 mutational changes, but conserved fold and catalytic residues, suggesting a role for dynamics in enzyme evolution. Here, we develop a conformational dynamics computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism. By deliberately weighting and altering the conformational dynamics of a putative Precambrian β-lactamase, we engineer enzyme specificity that mimics the modern TEM-1 β-lactamase with only 21 amino acid replacements. Our conformational dynamics design thus re-enacts the evolutionary process and provides a rational allosteric approach for manipulating function while conserving the enzyme active site.
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