ArticleStructure (London, England : 1993)2018
Chemical Crosslinking Mass Spectrometry Reveals the Conformational Landscape of the Activation Helix of PPARγ; a Model for Ligand-Dependent Antagonism.
Article in Structure (London, England : 1993), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- Structural determinants of non-covalent PPARγ inverse agonism and their therapeutic implications.Nature communications · 2025Article
- PPARγ modulator predictor (PGMP_v1): chemical space exploration and computational insights for enhanced type 2 diabetes mellitus management.Molecular diversity · 2025Article
- From Apo to Ligand-Bound: Unraveling PPARγ-LBD Conformational Shifts via Advanced Molecular Dynamics.ACS omega · 2025Article
- An integrative structural biology approach to identify the binding mode of a nanobody towards the pea ascorbate peroxidase.Computational and structural biotechnology journal · 2025Article
- Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
- Connexin Gap Junction Channels and Hemichannels: Insights from High-Resolution Structures.Biology · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Reduction in Obesity-Related Hepatic Fibrosis by SR1664.Biology · 2023Article
- Targeting the Alternative Vitamin E Metabolite Binding Site Enables Noncanonical PPARγ Modulation.Journal of the American Chemical Society · 2023Article
- Hydrogen-Deuterium Exchange Epitope Mapping of Glycosylated Epitopes Enabled by Online Immobilized Glycosidase.Analytical chemistry · 2023Article
- Fundamentals of HDX-MS.Essays in biochemistry · 2023Review
- Topological dynamics of an intrinsically disordered N-terminal domain of the human androgen receptor.Protein science : a publication of the Protein Society · 2022Article
- Analyzing the Androgen Receptor Interactome in Prostate Cancer: Implications for Therapeutic Intervention.Cells · 2022Review
- Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer.Medicinal research reviews · 2020Review
- A molecular switch regulating transcriptional repression and activation of PPARγ.Nature communications · 2020Article
- Peroxisome Proliferator-Activated Receptors: Experimental Targeting for the Treatment of Inflammatory Bowel Diseases.Frontiers in pharmacology · 2020Review
- An Integrated Approach for Determining a Protein-Protein Binding Interface in Solution and an Evaluation of Hydrogen-Deuterium Exchange Kinetics for Adjudicating Candidate Docking Models.Analytical chemistry · 2019Article
- The Plasma Factor XIII Heterotetrameric Complex Structure: Unexpected Unequal Pairing within a Symmetric Complex.Biomolecules · 2019Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Peroxisome proliferator-activated receptors (PPARs) are pharmacological targets for the treatment of metabolic disorders. Previously, we demonstrated the anti-diabetic effects of SR1664, a PPARγ modulator lacking classical transcriptional agonism, despite its poor pharmacokinetic properties. Here, we report identification of the antagonist SR11023 as a potent insulin sensitizer with significant plasma exposure following oral administration. To determine the structural mechanism of ligand-dependent antagonism of PPARγ, we employed an integrated approach combining solution-phase biophysical techniques to monitor activation helix (helix 12) conformational dynamics. While informative on receptor dynamics, hydrogen/deuterium exchange mass spectrometry and nuclear magnetic resonance data provide limited information regarding the specific orientations of structural elements. In contrast, label-free quantitative crosslinking mass spectrometry revealed that binding of SR11023 to PPARγ enhances interaction with co-repressor motifs by pushing H12 away from the agonist active conformation toward the H2-H3 loop region (i.e., the omega loop), revealing the molecular mechanism for active antagonism of PPARγ.
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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.