ArticleNature communications2016
A substrate-driven allosteric switch that enhances PDI catalytic activity.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 124 citations in OpenAlex.
- Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.JCI insight · 2019Trial
- Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation.JCI insight · 2017Trial
- Molecular mechanisms of protein disulfide isomerase antagonism by punicalagin.Biochemical and biophysical research communications · 2026Article
- Article
- Enzyme-Inspired Design of Redox-Active Molecules for Promotion of Oxidative Protein Folding.Chembiochem : a European journal of chemical biology · 2026Review
- Systematic determination of disulfide bond reduction potentials reveals a nonequilibrium redox hierarchy in cyanobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular insights into protein disulfide isomerase antagonism by punicalagin.bioRxiv : the preprint server for biology · 2026Article
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- Workflow for Accurate Measurement of PDI Reductase Kinetics Using a Fluorescent Disulfide Substrate.microPublication biology · 2026Article
- Determining the Redox Potential of a Protein Disulfide Bond.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Assays of Thiol Isomerase Activity.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- Galloylated polyphenols represent a new class of antithrombotic agents with broad activity against thiol isomerases.Journal of thrombosis and haemostasis : JTH · 2025Article
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- Mechanistic basis of activation and inhibition of protein disulfide isomerase by allosteric antithrombotic compounds.Journal of thrombosis and haemostasis : JTH · 2025Article
- Decoding PDI diversity: Insights into structure, domains, and functionality in sorghum.Computational and structural biotechnology journal · 2025Article
- Protein disulfide isomerase A1 regulates fenestration dynamics in primary mouse liver sinusoidal endothelial cells (LSECs).Redox biology · 2024Article
- Protein disulfide isomerase uses thrombin-antithrombin complex as a template to bind its target protein and alter the blood coagulation rates.Bioscience reports · 2024Article
- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein disulfide isomerase (PDI) is an oxidoreductase essential for folding proteins in the endoplasmic reticulum. The domain structure of PDI is a-b-b'-x-a', wherein the thioredoxin-like a and a' domains mediate disulfide bond shuffling and b and b' domains are substrate binding. The b' and a' domains are connected via the x-linker, a 19-amino-acid flexible peptide. Here we identify a class of compounds, termed bepristats, that target the substrate-binding pocket of b'. Bepristats reversibly block substrate binding and inhibit platelet aggregation and thrombus formation in vivo. Ligation of the substrate-binding pocket by bepristats paradoxically enhances catalytic activity of a and a' by displacing the x-linker, which acts as an allosteric switch to augment reductase activity in the catalytic domains. This substrate-driven allosteric switch is also activated by peptides and proteins and is present in other thiol isomerases. Our results demonstrate a mechanism whereby binding of a substrate to thiol isomerases enhances catalytic activity of remote domains.
Indexed as
Identifiers
What 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.