ArticlePLoS biology2010
Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 2 of them syntheses that pooled it.
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Who cites it
158 citing papers in PubMed, 2 syntheses or guidelines pooled it, 299 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Broad-Spectrum Antiviral Activity of Cyclophilin Inhibitors Against Coronaviruses: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- A non-catalytic interaction surface mediates recognition of spliceosomal factors by the Toxoplasma gondii cyclophilin TgCyp23.The Biochemical journal · 2026Article
- Development of Benzothiophene-Bearing Bis-oxadiazole Derivatives for Potential Anticancer Targets: Evaluation of DFT, ADME-Tox, and In Silico Docking.Chemistry & biodiversity · 2026Article
- Genetic Drivers of Sensitivity or Resistance to RAS(ON) Multiselective Inhibitors in NRAS-Mutated Melanoma.Cancer research · 2026Article
- Machine learning-driven investigation on liquid-liquid phase separation-related prognostic signature in diffuse large B-cell lymphoma.British journal of haematology · 2026Article
- An Atlas of Short Linear Motif-Mediated Human Protein-Protein Interactions.bioRxiv : the preprint server for biology · 2026Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Structural and Kinetic Variability of Pathogen Cyclophilins: Functional Diversification and Therapeutic Potential.ACS infectious diseases · 2026Review
- Biophysical characterization of Cyclophilin B reveals membrane localization as its primary functional determinant as a prolyl isomerase.Protein science : a publication of the Protein Society · 2026Article
- Identification of glycometabolism-related genes for predicting the prognosis of patients with glioblastoma and its correlation with immune infiltration.Discover oncology · 2026Article
- Cyclophilin A stabilizes the capsid protein p72 to facilitate African swine fever virus replication.Nature communications · 2026Article
- IgE to cyclophilin Bet v 7 triggers mast cell activation and mediates cross-reactivity with Ara h 18 in children with seasonal allergic rhinitis.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Structural adaptability of SARS-CoV-2 Nsp1 with the host network.European biophysics journal : EBJ · 2026Article
- Construction of Bovine CypA Gene Expression Vector and Validation of Its Expression in CHO-K1 Cells.Animals : an open access journal from MDPI · 2026Article
- PPIA regulates fatty acid and glutamine metabolism in lung adenocarcinoma based on multiomics prognostic model and experiment validation.Scientific reports · 2026Article
- All-atom molecular dynamics simulation of Cyclophilin A in complex with Sanglifehrin A.PloS one · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Pushing the limits of hydrogen/deuterium exchange mass spectrometry to study protein:fragment low affinity interactions.Communications chemistry · 2025Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known for being the target of the immunosuppressive drug cyclosporin, used to combat organ transplant rejection. There is great interest in both the substrate specificity of these enzymes and the design of isoform-selective ligands for them. However, the dearth of available data for individual family members inhibits attempts to design drug specificity; additionally, in order to define physiological functions for the cyclophilins, definitive isoform characterization is required. In the current study, enzymatic activity was assayed for 15 of the 17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold was tested. In order to rationalize the observed isoform diversity, the high-resolution crystallographic structures of seven cyclophilin domains were determined. These models, combined with seven previously solved cyclophilin isoforms, provide the basis for a family-wide structure:function analysis. Detailed structural analysis of the human cyclophilin isomerase explains why cyclophilin activity against short peptides is correlated with an ability to ligate cyclosporin and why certain isoforms are not competent for either activity. In addition, we find that regions of the isomerase domain outside the proline-binding surface impart isoform specificity for both in vivo substrates and drug design. We hypothesize that there is a well-defined molecular surface corresponding to the substrate-binding S2 position that is a site of diversity in the cyclophilin family. Computational simulations of substrate binding in this region support our observations. Our data indicate that unique isoform determinants exist that may be exploited for development of selective ligands and suggest that the currently available small-molecule and peptide-based ligands for this class of enzyme are insufficient for isoform specificity.
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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.