ArticleBiology2014
A Structural Switch between Agonist and Antagonist Bound Conformations for a Ligand-Optimized Model of the Human Aryl Hydrocarbon Receptor Ligand Binding Domain.
Article in Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- AhR as a Common Denominator in Immunity and Inflammation in Chronic Lung Diseases: Molecular and Clinical Insights.Diseases (Basel, Switzerland) · 2026Review
- Exploration of Agonist and Antagonist Binding Sites within the Cytosolic AHR Complex Using Molecular Modeling.ACS omega · 2026Article
- Alizarin, an Agonist of AHR Receptor, Enhances CYP1A1 Enzyme Activity and Induces Transcriptional Changes in Hepatoma Cells.Molecules (Basel, Switzerland) · 2023Article
- Aryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey.Molecules (Basel, Switzerland) · 2023Review
- OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.Nature chemistry · 2023Article
- Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer.Biology · 2023Review
- The pharmacokinetics profiles, pharmacological properties, and toxicological risks of dehydroevodiamine: A review.Frontiers in pharmacology · 2022Review
- Ah receptor ligands and their impacts on gut resilience: structure-activity effects.Critical reviews in toxicology · 2020Review
- Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.Journal of clinical medicine · 2020Article
- PCB126 blocks the thermogenic beiging response of adipocytes.Environmental science and pollution research international · 2020Article
- Article
- The Henna pigment Lawsone activates the Aryl Hydrocarbon Receptor and impacts skin homeostasis.Scientific reports · 2019Article
- Modeling the binding of diverse ligands within the Ah receptor ligand binding domain.Scientific reports · 2019Article
- Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells.Scientific reports · 2019Article
- Structure-Activity Relationships of the Main Bioactive Constituents ofDrug metabolism and disposition: the biological fate of chemicals · 2018Article
- TCDD, FICZ, and Other High Affinity AhR Ligands Dose-Dependently Determine the Fate of CD4+ T Cell Differentiation.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target.Archives of toxicology · 2017Review
- Mechanistic Investigations Into the Developmental Toxicity of Nitrated and Heterocyclic PAHs.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations.Environmental health perspectives · 2017Article
- Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms.Current opinion in toxicology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of a diverse group of genes. Exogenous AHR ligands include the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent agonist, and the synthetic AHR antagonist N-2-(1H-indol-3yl)ethyl)-9-isopropyl-2- (5-methylpyridin-3-yl)-9H-purin-6-amine (GNF351). As no experimentally determined structure of the ligand binding domain exists, homology models have been utilized for virtual ligand screening (VLS) to search for novel ligands. Here, we have developed an "agonist-optimized" homology model of the human AHR ligand binding domain, and this model aided in the discovery of two human AHR agonists by VLS. In addition, we performed molecular dynamics simulations of an agonist TCDD-bound and antagonist GNF351-bound version of this model in order to gain insights into the mechanics of the AHR ligand-binding pocket. These simulations identified residues 307-329 as a flexible segment of the AHR ligand pocket that adopts discrete conformations upon agonist or antagonist binding. This flexible segment of the AHR may act as a structural switch that determines the agonist or antagonist activity of a given AHR ligand.
Identifiers
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.