ArticleBMC evolutionary biology2008
Evolution of pharmacologic specificity in the pregnane X receptor.
Article in BMC evolutionary biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 108 citations in OpenAlex.
- Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.Nature structural & molecular biology · 2025Article
- Metabolic disrupting chemicals in the intestine: the need for biologically relevant models: Zebrafish: what can we learn from this small environment-sensitive fish?FEBS open bio · 2024Review
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids UsingFrontiers in endocrinology · 2021Article
- Vitamin K in Vertebrates' Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species.Biomolecules · 2020Review
- CRISPR-Cas9-Mutated Pregnane X Receptor (pxr) Retains Pregnenolone-induced Expression of cyp3a65 in Zebrafish (Danio rerio) Larvae.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos.Environmental science and pollution research international · 2020Article
- Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity.International journal of molecular sciences · 2019Article
- Sequence Variations in pxr (nr1i2) From Zebrafish (Danio rerio) Strains Affect Nuclear Receptor Function.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Evolutionary Perspective in Rickets and Vitamin D.Frontiers in endocrinology · 2019Review
- Independent losses of a xenobiotic receptor across teleost evolution.Scientific reports · 2018Article
- Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents.Environmental pollution (Barking, Essex : 1987) · 2018Article
- Evolutionary Origin of the Interferon-Immune Metabolic Axis: The Sterol-Vitamin D Link.Frontiers in immunology · 2017Article
- Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity.Biochimica et biophysica acta · 2016Article
- Evolutionary and Functional Diversification of the Vitamin D Receptor-Lithocholic Acid Partnership.PloS one · 2016Article
- BFCOD activity in fish cell lines and zebrafish embryos and its modulation by chemical ligands of human aryl hydrocarbon and nuclear receptors.Environmental science and pollution research international · 2015Article
- Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.Nature communications · 2015Article
- Zebrafish vitamin K epoxide reductases: expression in vivo, along extracellular matrix mineralization and under phylloquinone and warfarin in vitro exposure.Fish physiology and biochemistry · 2015Article
- Environmental contaminants activate human and polar bear (Ursus maritimus) pregnane X receptors (PXR, NR1I2) differently.Toxicology and applied pharmacology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe pregnane X receptor (PXR) shows the highest degree of cross-species sequence diversity of any of the vertebrate nuclear hormone receptors. In this study, we determined the pharmacophores for activation of human, mouse, rat, rabbit, chicken, and zebrafish PXRs, using a common set of sixteen ligands. In addition, we compared in detail the selectivity of human and zebrafish PXRs for steroidal compounds and xenobiotics. The ligand activation properties of the Western clawed frog (Xenopus tropicalis) PXR and that of a putative vitamin D receptor (VDR)/PXR cloned in this study from the chordate invertebrate sea squirt (Ciona intestinalis) were also investigated.
resultsUsing a common set of ligands, human, mouse, and rat PXRs share structurally similar pharmacophores consisting of hydrophobic features and widely spaced excluded volumes indicative of large binding pockets. Zebrafish PXR has the most sterically constrained pharmacophore of the PXRs analyzed, suggesting a smaller ligand-binding pocket than the other PXRs. Chicken PXR possesses a symmetrical pharmacophore with four hydrophobes, a hydrogen bond acceptor, as well as excluded volumes. Comparison of human and zebrafish PXRs for a wide range of possible activators revealed that zebrafish PXR is activated by a subset of human PXR agonists. The Ciona VDR/PXR showed low sequence identity to vertebrate VDRs and PXRs in the ligand-binding domain and was preferentially activated by planar xenobiotics including 6-formylindolo-[3,2-b]carbazole. Lastly, the Western clawed frog (Xenopus tropicalis) PXR was insensitive to vitamins and steroidal compounds and was activated only by benzoates.
conclusionIn contrast to other nuclear hormone receptors, PXRs show significant differences in ligand specificity across species. By pharmacophore analysis, certain PXRs share similar features such as human, mouse, and rat PXRs, suggesting overlap of function and perhaps common evolutionary forces. The Western clawed frog PXR, like that described for African clawed frog PXRs, has diverged considerably in ligand selectivity from fish, bird, and mammalian PXRs.
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