ArticleACS chemical biology2016
Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1.
Article in ACS chemical biology, 2016. 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, 87 citations in OpenAlex.
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- Transcriptional Control of Lipid Metabolism.Advances in experimental medicine and biology · 2026Review
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Identification and Validation of Inverse Agonists for Nuclear Receptor Subfamily 4 Group A Member 2.ACS omega · 2025Article
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- The endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors.British journal of pharmacology · 2025Article
- A Nurr1 Agonist Derived from the Natural Ligand DHI Induces Neuroprotective Gene Expression.Journal of medicinal chemistry · 2025Article
- Review
- Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing.Communications chemistry · 2024Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- Article
- Exploring Fatty Acid Mimetics as NR4A Ligands.Journal of medicinal chemistry · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Simple purification of small-molecule-labelled peptidesChemical science · 2023Article
- Flavone and Hydroxyflavones Are Ligands That Bind the Orphan Nuclear Receptor 4A1 (NR4A1).International journal of molecular sciences · 2023Article
- Article
- Prostaglandin A2 Interacts with Nurr1 and Ameliorates Behavioral Deficits in Parkinson's Disease Fly Model.Neuromolecular medicine · 2022Article
- The role of NURR1 in metabolic abnormalities of Parkinson's disease.Molecular neurodegeneration · 2022Review
- Article
- Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries.ChemMedChem · 2022Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Nurr1/NR4A2 is an orphan nuclear receptor, and currently there are no known natural ligands that bind Nurr1. A recent metabolomics study identified unsaturated fatty acids, including arachidonic acid and docosahexaenoic acid (DHA), that interact with the ligand-binding domain (LBD) of a related orphan receptor, Nur77/NR4A1. However, the binding location and whether these ligands bind other NR4A receptors were not defined. Here, we show that unsaturated fatty acids also interact with the Nurr1 LBD, and solution NMR spectroscopy reveals the binding epitope of DHA at its putative ligand-binding pocket. Biochemical assays reveal that DHA-bound Nurr1 interacts with high affinity with a peptide derived from PIASγ, a protein that interacts with Nurr1 in cellular extracts, and DHA also affects cellular Nurr1 transactivation. This work is the first structural report of a natural ligand binding to a canonical NR4A ligand-binding pocket and indicates a natural ligand can bind and affect Nurr1 function.
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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.