ArticleNature communications2020
Altered conformational sampling along an evolutionary trajectory changes the catalytic activity of an enzyme.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 64 citations in OpenAlex.
- Distinct energetic blueprints diversify function of conserved protein folds.Nature chemistry · 2026Article
- Large-scale protein conformational transitions revealed by weighted ensemble simulations and EPR.Chemical science · 2026Article
- Multidomain DNA-Protein Mining Reveals Polymorphic Variations in RhlB Enhancing Monorhamnolipid Biosynthesis.ACS synthetic biology · 2026Article
- Structural and evolutionary constraints of organophosphate resistance in dipteran carboxylesterases.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Conformational Dynamics and Catalytic Backups in a Hyper-thermostable Engineered Archaeal Protein Tyrosine Phosphatase.JACS Au · 2026Article
- A Three-Module Machine Learning Framework for Protein Sequence- and Temperature-DependentACS synthetic biology · 2025Article
- Accurate Protein Dynamic Conformational Ensembles: Combining AlphaFold, MD, and AmideInternational journal of molecular sciences · 2025Article
- GArNet: A Genetic Algorithm-Based Protein Redesign Approach to Optimize Mutation Combinations Informed by Network Theory.Journal of chemical information and modeling · 2025Article
- Protein Modeling with DEER Spectroscopy.Annual review of biophysics · 2025Review
- Ancestral Reconstruction and the Evolution of Protein Energy Landscapes.Annual review of biophysics · 2024Review
- Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.Cell systems · 2024Article
- Computational remodeling of an enzyme conformational landscape for altered substrate selectivity.Nature communications · 2023Article
- Enzymatic Conjugation of Modified RNA Fragments by Ancestral RNA Ligase AncT4_2.Applied and environmental microbiology · 2022Article
- Targeting protein conformations with small molecules to control protein complexes.Trends in biochemical sciences · 2022Review
- The role of oligomerization in the optimization of cyclohexadienyl dehydratase conformational dynamics and catalytic activity.Protein science : a publication of the Protein Society · 2022Article
- Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation.Nature communications · 2022Article
- Temperature-dependent hydrogen deuterium exchange shows impact of analog binding on adenosine deaminase flexibility but not embedded thermal networks.The Journal of biological chemistry · 2022Article
- Leveraging intrinsic flexibility to engineer enhanced enzyme catalytic activity.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Distal Mutations Shape Substrate-Binding Sites during Evolution of a Metallo-Oxidase into a Laccase.ACS catalysis · 2022Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several enzymes are known to have evolved from non-catalytic proteins such as solute-binding proteins (SBPs). Although attention has been focused on how a binding site can evolve to become catalytic, an equally important question is: how do the structural dynamics of a binding protein change as it becomes an efficient enzyme? Here we performed a variety of experiments, including propargyl-DO3A-Gd(III) tagging and double electron-electron resonance (DEER) to study the rigid body protein dynamics of reconstructed evolutionary intermediates to determine how the conformational sampling of a protein changes along an evolutionary trajectory linking an arginine SBP to a cyclohexadienyl dehydratase (CDT). We observed that primitive dehydratases predominantly populate catalytically unproductive conformations that are vestiges of their ancestral SBP function. Non-productive conformational states, including a wide-open state, are frozen out of the conformational landscape via remote mutations, eventually leading to extant CDT that exclusively samples catalytically relevant compact states. These results show that remote mutations can reshape the global conformational landscape of an enzyme as a mechanism for increasing catalytic activity.
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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.