ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2018
Ancient thioredoxins evolved to modern-day stability-function requirement by altering native state ensemble.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Unveiling the thioredoxin fold: a systematic review and bioinformatic analysis of protein disulfide isomerase and Dsb family proteins.Frontiers in bioinformatics · 2026Pooled it
- Topological metrics as evolutionary and dynamical descriptors of conformational landscapes within protein families.PLoS computational biology · 2026Article
- Trp101-Mediated Cold Adaptation inACS omega · 2025Article
- Dynamic Allostery: Evolution's Double-Edged Sword in Protein Function and Disease.Journal of molecular biology · 2025Review
- Statistical Physics-Based Approaches to Model the Function and Complexation of Disordered Proteins.The journal of physical chemistry. B · 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
- Aromatic Residue Variations in the Central β‑Sheet Influence Stability and Activity of E. coli Glutaredoxin 3.ACS omega · 2025Article
- Structural Adaptations of Bacterial Grx3 to Temperature: Pro29 Is Essential for Cold Adaptation inACS omega · 2025Article
- Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease.Antioxidants & redox signaling · 2025Review
- Trp31 Residue of Trx-1 Is Essential for Maintaining Antioxidant Activity and Cellular Redox Defense Against Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Reduced Thioredoxin Regulates IL-1β Secretion via NLRP3 of IL-1β+ Alveolar Macrophages in COPD.Journal of inflammation research · 2025Article
- Serum T2-High Inflammation Mediators in Eosinophilic COPD.Biomolecules · 2024Article
- Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria.Science advances · 2024Article
- Thr-to-Ala Mutation Leads to a Larger Aromatic Pair and Reduced Packing Density in α1,α3-Helices during Thioredoxin Cold Adaptation.ACS omega · 2024Article
- Role of thioredoxin in chronic obstructive pulmonary disease (COPD): a promising future target.Respiratory research · 2023Review
- Conformational Tuning Shapes the Balance between Functional Promiscuity and Specialization in ParalogousBiochemistry · 2023Article
- Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023Article
- Protein dynamics provide mechanistic insights about epistasis among common missense polymorphisms.Biophysical journal · 2023Article
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4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thioredoxins (THRXs)-small globular proteins that reduce other proteins-are ubiquitous in all forms of life, from Archaea to mammals. Although ancestral thioredoxins share sequential and structural similarity with the modern-day (extant) homologues, they exhibit significantly different functional activity and stability. We investigate this puzzle by comparative studies of their (ancient and modern-day THRXs') native state ensemble, as quantified by the dynamic flexibility index (DFI), a metric for the relative resilience of an amino acid to perturbations in the rest of the protein. Clustering proteins using DFI profiles strongly resemble an alternative classification scheme based on their activity and stability. The DFI profiles of the extant proteins are substantially different around the α3, α4 helices and catalytic regions. Likewise, allosteric coupling of the active site with the rest of the protein is different between ancient and extant THRXs, possibly explaining the decreased catalytic activity at low pH with evolution. At a global level, we note that the population of low-flexibility (called hinges) and high-flexibility sites increases with evolution. The heterogeneity (quantified by the variance) in DFI distribution increases with the decrease in the melting temperature typically associated with the evolution of ancient proteins to their modern-day counterparts.This article is part of a discussion meeting issue 'Allostery and molecular machines'.
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