ArticleInternational journal of molecular sciences2018
Comparative In Vitro and In Silico Analysis of the Selectivity of Indirubin as a Human Ah Receptor Agonist.
Article in International journal of molecular sciences, 2018. 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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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Exploration of Agonist and Antagonist Binding Sites within the Cytosolic AHR Complex Using Molecular Modeling.ACS omega · 2026Article
- Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex.Nature communications · 2025Article
- The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The aryl hydrocarbon receptor differentially modulates the expression profile of antibody isotypes in a human B-cell line.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Evolutive emergence and divergence of an Ig regulatory node: An environmental sensor getting cues from the aryl hydrocarbon receptor?Frontiers in immunology · 2023Review
- Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex.Nature communications · 2022Article
- Review
- Curcumin Facilitates Aryl Hydrocarbon Receptor Activation to Ameliorate Inflammatory Astrogliosis.Molecules (Basel, Switzerland) · 2022Article
- The aryl hydrocarbon receptor: A predominant mediator for the toxicity of emerging dioxin-like compounds.Journal of hazardous materials · 2022Review
- Editorial: Role of the Aryl Hydrocarbon Receptor in Immune Modulation.Frontiers in toxicology · 2022Article
- Refinement of coding SNPs in the human aryl hydrocarbon receptor gene using ISNPranker: An integrative-SNP ranking web-tool.Computational biology and chemistry · 2021Article
- AhR and Cancer: From Gene Profiling to Targeted Therapy.International journal of molecular sciences · 2021Review
- The Cellular and Molecular Determinants of Naphthoquinone-Dependent Activation of the Aryl Hydrocarbon Receptor.International journal of molecular sciences · 2020Article
- A Biomimetic, One-Step Transformation of Simple Indolic Compounds toChemical research in toxicology · 2019Article
- Modeling the binding of diverse ligands within the Ah receptor ligand binding domain.Scientific reports · 2019Article
- Urolithin A Is a Dietary Microbiota-Derived Human Aryl Hydrocarbon Receptor Antagonist.Metabolites · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that modulates gene expression following its binding and activation by structurally diverse chemicals. Species differences in AhR functionality have been observed, with the mouse AhR (mAhR) and human AhR (hAhR) exhibiting significant differences in ligand binding, coactivator recruitment, gene expression and response. While the AhR agonist indirubin (IR) is a more potent activator of hAhR-dependent gene expression than the prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), it is a significantly less potent activator of the mAhR. DNA binding analysis confirmed the greater potency/efficacy of IR in stimulating transformation/DNA binding of the hAhR in vitro and domain-swapping experiments demonstrated that the enhanced response to IR was primarily due to the hAhR ligand binding domain (LBD). Site-directed mutagenesis and functional analysis studies revealed that mutation of H326 and A349 in the mAhR LBD to the corresponding residues in the hAhR LBD significantly increased the potency of IR. Since these mutations had no significant effect on ligand binding, these residues likely contribute to an enhanced efficiency of transformation/DNA binding by IR-bound hAhR. Molecular docking to mAhR LBD homology models further elucidated the different roles of the A375V mutation in TCDD and IR binding, as revealed by [³H]TCDD competitive binding results. These results demonstrate the differential binding of structurally diverse ligands within the LBD of a given AhR and confirm that amino acid differences within the LBD of AhRs contribute to significant species differences in ligand response.
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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.