ArticleMolecular pharmacology2017
Structural Analysis of the Glucocorticoid Receptor Ligand-Binding Domain in Complex with Triamcinolone Acetonide and a Fragment of the Atypical Coregulator, Small Heterodimer Partner.
Article in Molecular pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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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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
16 citing papers in PubMed, 24 citations in OpenAlex.
- A four‑gene signature identifies TKI‑induced persister cells and uncovers a ZLN005‑induced pyroptotic vulnerability via the GSDME pathway in EGFR‑mutant lung cancer.Molecular medicine reports · 2026Article
- Human DRG Glucocorticoid Receptor Profiling Reveals Targets for Regionally Delivered Steroid Analgesia.Cells · 2026Article
- Article
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities.Nucleic acids research · 2022Article
- Role of microRNAs and long non‑coding RNAs in glucocorticoid signaling (Review).International journal of molecular medicine · 2022Review
- The Role of Conformational Dynamics and Allostery in the Control of Distinct Efficacies of Agonists to the Glucocorticoid Receptor.Frontiers in molecular biosciences · 2022Article
- Structural insights into glucocorticoid receptor function.Biochemical Society transactions · 2021Review
- Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GAS5‑mediated regulation of cell signaling (Review).Molecular medicine reports · 2020Review
- Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Systemic Effects by Intrathecal Administration of Triamcinolone Acetonide in Patients With Multiple Sclerosis.Frontiers in endocrinology · 2020Article
- First High-Resolution Crystal Structures of the Glucocorticoid Receptor Ligand-Binding Domain-Peroxisome Proliferator-ActivatedMolecular pharmacology · 2019Article
- Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Nucleotide Binding to ARL2 in the TBCD∙ARL2∙β-Tubulin Complex Drives Conformational Changes in β-Tubulin.Journal of molecular biology · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The synthetic glucocorticoids (GCs) dexamethasone, mometasone furoate, and triamcinolone acetonide are pharmaceutical mainstays to treat chronic inflammatory diseases. These drugs bind to the glucocorticoid receptor (GR), a ligand-activated transcription factor and member of the nuclear receptor superfamily. The GR is widely recognized as a therapeutic target for its ability to counter proinflammatory signaling. Despite the popularity of GCs in the clinic, long-term use leads to numerous side effects, driving the need for new and improved drugs with less off-target pharmacology. X-ray crystal structures have played an important role in the drug-design process, permitting the characterization of robust structure-function relationships. However, steroid receptor ligand-binding domains (LBDs) are inherently unstable, and their crystallization requires extensive mutagenesis to enhance expression and crystallization. Here, we use an ancestral variant of GR as a tool to generate a high-resolution crystal structure of GR in complex with the potent glucocorticoid triamcinolone acetonide (TA) and a fragment of the small heterodimer partner (SHP). Using structural analysis, molecular dynamics, and biochemistry, we show that TA increases intramolecular contacts within the LBD to drive affinity and enhance stability of the receptor-ligand complex. These data support the emerging theme that ligand-induced receptor conformational dynamics at the mouth of the pocket play a major role in steroid receptor activation. This work also represents the first GR structure in complex with SHP, which has been suggested to play a role in modulating hepatic GR 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.