ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cyclophilin A catalyzes proline isomerization by an electrostatic handle mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed.
- Towards next generation enzyme mimics through local electric field control in organic cage catalysts.Chemical science · 2026Article
- Generalizing the Gaussian Network Model: Spanning-Tree Thermodynamics Shows Entropy-Driven KRAS Activation.Proteins · 2026Article
- Cyclophilin A-mediated cis/trans isomerization modulates RIN4 to control intracellular rhizobial infection in legumes.The New phytologist · 2026Article
- All-atom molecular dynamics simulation of Cyclophilin A in complex with Sanglifehrin A.PloS one · 2026Article
- Force writes memory: proline isomerization as a molecular memory switch.Biochemical Society transactions · 2025Review
- Potent Preorganized Pyrazolidine Cyclophilin D Inhibitors Prevent Mitochondrial and Organ Injury in a Mouse Pancreatitis Disease Model.Journal of medicinal chemistry · 2025Article
- Single-molecule nanopore sensing of prolineChemical science · 2025Article
- An integrative characterization of proline cis and trans conformers in a disordered peptide.Biophysical journal · 2024Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A.Current research in structural biology · 2024Article
- Peptidyl Prolyl Isomerase A Modulates the Liquid-Liquid Phase Separation of Proline-Rich IDPs.Journal of the American Chemical Society · 2022Article
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Dynamic design: manipulation of millisecond timescale motions on the energy landscape of cyclophilin A.Chemical science · 2020Article
- Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques.Frontiers in cell and developmental biology · 2020Review
- Mutagenesis computer experiments in pentameric ligand-gated ion channels: the role of simulation tools with different resolution.Interface focus · 2019Review
- Exosomal cyclophilin A as a novel noninvasive biomarker for Epstein-Barr virus associated nasopharyngeal carcinoma.Cancer medicine · 2019Article
- A Biophysical Perspective on Enzyme Catalysis.Biochemistry · 2019Article
- Structural insight into prolineThe Journal of biological chemistry · 2018Article
- X-ray structure of alisporivir in complex with cyclophilin A at 1.5 Å resolution.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Rescue of conformational dynamics in enzyme catalysis by directed evolution.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Proline isomerization is a ubiquitous process that plays a key role in the folding of proteins and in the regulation of their functions. Different families of enzymes, known as "peptidyl-prolyl isomerases" (PPIases), catalyze this reaction, which involves the interconversion between the cis and trans isomers of the N-terminal amide bond of the amino acid proline. However, complete descriptions of the mechanisms by which these enzymes function have remained elusive. We show here that cyclophilin A, one of the most common PPIases, provides a catalytic environment that acts on the substrate through an electrostatic handle mechanism. In this mechanism, the electrostatic field in the catalytic site turns the electric dipole associated with the carbonyl group of the amino acid preceding the proline in the substrate, thus causing the rotation of the peptide bond between the two residues. We identified this mechanism using a combination of NMR measurements, molecular dynamics simulations, and density functional theory calculations to simultaneously determine the cis-bound and trans-bound conformations of cyclophilin A and its substrate as the enzymatic reaction takes place. We anticipate that this approach will be helpful in elucidating whether the electrostatic handle mechanism that we describe here is common to other PPIases and, more generally, in characterizing other enzymatic processes.
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.