ArticleStructure (London, England : 1993)2021
Structural mechanism underlying ligand binding and activation of PPARγ.
Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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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.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Dosing PPARγ Activation With Light Using Fast Relaxing Photoswitches.Angewandte Chemie (International ed. in English) · 2026Article
- Peroxisome proliferator-activated receptor gamma (PPARγ) as a mechano-metabolic transducer: coordinating lipid homeostasis through mechanical cues.Molecular biomedicine · 2026Review
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin fromJournal of agricultural and food chemistry · 2026Article
- Enhancing Maize Drought Resilience with Agrichar Soil Amendments and Nanobiochar Foliar Sprays: Effects on Physio-Biochemical Responses.ACS omega · 2026Article
- Anabolic-Androgenic Steroids Revisited: Structural Biology, Receptor Signaling, and Mechanisms of Anabolic-Androgenic Dissociation.International journal of molecular sciences · 2026Review
- Article
- Small molecule inhibitor of PPARγ acetylation promotes insulin sensitization and browning of white adipose tissue with improved safety.bioRxiv : the preprint server for biology · 2025Article
- From Apo to Ligand-Bound: Unraveling PPARγ-LBD Conformational Shifts via Advanced Molecular Dynamics.ACS omega · 2025Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- Modulation of Protein-Protein Interactions with Molecular Glues in a Synthetic Condensate Platform.Journal of the American Chemical Society · 2025Article
- Discovery of a novel binding pocket in PPARγ for partial agonists: structure-based virtual screening identifies ginsenoside Rg5 as a partial agonist promoting beige adipogenesis.Frontiers in chemistry · 2025Article
- Agonists of the Nuclear Receptor PPARγ Can Produce Biased Signaling.Molecular pharmacology · 2024Article
- Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
- Cladosporols and PPARγ: Same Gun, Same Bullet, More Targets.Biomolecules · 2024Review
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.bioRxiv : the preprint server for biology · 2024Article
- PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.Biomolecules · 2024Review
- Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma.International journal of molecular sciences · 2023Article
- Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease.Biomedicines · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Ligands bind to an occluded orthosteric ligand-binding pocket within the nuclear receptor ligand-binding domain. Molecular simulations have revealed theoretical ligand entry/exit pathways to the orthosteric pocket; however, it remains unclear whether ligand binding proceeds through induced fit or conformational selection mechanisms. Here, using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry, and surface plasmon resonance analysis, we provide evidence that structurally distinct agonists bind peroxisome proliferator-activated receptor γ (PPARγ) via a two-step induced fit mechanism involving an initial fast kinetic step followed by a slow conformational change. The agonist encounter complex binding pose is suggested in crystal structures where ligands bind to a surface pore suggested as a ligand entry site in molecular simulations. Our findings suggest an activation mechanism for PPARγ whereby agonist binding occurs through an initial encounter complex followed by a transition of the ligand into the final binding pose within the orthosteric pocket, inducing a transcriptionally active conformation.
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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.