ArticleNature chemistry2021
Evolution of dynamical networks enhances catalysis in a designer enzyme.
Article in Nature chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed.
- Protein Structuromics Reveals a Loop-Controlled Half-Open Active Pocket Conformation Throughout Fe(II)/α-ketoglutarate-Dependent Dioxygenase Catalytic Cycle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Activation parameters, enthalpy-entropy compensation and the temperature-dependent activity of enzymes.Protein science : a publication of the Protein Society · 2026Article
- Emergence of specific binding and catalysis from a designed generalist binding protein.Nature chemistry · 2026Article
- Creating highly active fluoroacetate dehalogenases via gate-based synergetic chain design.Nature communications · 2026Article
- Conformational Dynamics and Catalytic Backups in a Hyper-thermostable Engineered Archaeal Protein Tyrosine Phosphatase.JACS Au · 2026Article
- A Structural Landscape Depiction of Dynamic Stability Centers of Local Structure in Protein Thermostability Engineering.Research (Washington, D.C.) · 2026Article
- Article
- Approaches for regulating enzyme activities: Recent advances in experiment and computation.Current opinion in structural biology · 2025Review
- Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release.Nature communications · 2025Article
- Caver Web 2.0: analysis of tunnels and ligand transport in dynamic ensembles of proteins.Nucleic acids research · 2025Article
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Computational design of serine hydrolases.Science (New York, N.Y.) · 2025Article
- Physics-based modeling in the new era of enzyme engineering.Nature computational science · 2025Review
- Characterization of a NaWorld journal of microbiology & biotechnology · 2025Article
- Machine Learning Guided Rational Design of a Non-Heme Iron-Based Lysine Dioxygenase Improves its Total Turnover Number.Chembiochem : a European journal of chemical biology · 2024Article
- 3D variability analysis reveals a hidden conformational change controlling ammonia transport in human asparagine synthetase.Nature communications · 2024Article
- Using residue interaction networks to understand protein function and evolution and to engineer new proteins.Current opinion in structural biology · 2024Review
- The Evolution of the Acylation Mechanism inACS catalysis · 2024Article
- Harnessing conformational dynamics in enzyme catalysis to achieve nature-like catalytic efficiencies: the shortest path map tool for computational enzyme redesign.Faraday discussions · 2024Article
- Computation-guided engineering of distal mutations in an artificial enzyme.Faraday discussions · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Activation heat capacity is emerging as a crucial factor in enzyme thermoadaptation, as shown by the non-Arrhenius behaviour of many natural enzymes. However, its physical origin and relationship to the evolution of catalytic activity remain uncertain. Here we show that directed evolution of a computationally designed Kemp eliminase reshapes protein dynamics, which gives rise to an activation heat capacity absent in the original design. These changes buttress transition-state stabilization. Extensive molecular dynamics simulations show that evolution results in the closure of solvent-exposed loops and a better packing of the active site. Remarkably, this gives rise to a correlated dynamical network that involves the transition state and large parts of the protein. This network tightens the transition-state ensemble, which induces a negative activation heat capacity and non-linearity in the activity-temperature dependence. Our results have implications for understanding enzyme evolution and suggest that selectively targeting the conformational dynamics of the transition-state ensemble by design and evolution will expedite the creation of novel enzymes.
Indexed as
Identifiers
34413499What OpenQuestion holds
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.