Cited by 489Toxic Organic Pollutants ImpactPharmacogenetics and Drug MetabolismCarcinogens and Genotoxicity Assessment

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Ligand binding and activation of the Ah receptor

Denison, Michael S, Pandini, Alessandro, Nagy, Scott R, Baldwin, Enoch P, Bonati, Laura·2002·Chemico-Biological Interactions

DOI 10.1016/s0009-2797(02)00063-7

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Abstract

The Ah receptor (AhR) is a ligand-dependent transcription factor that can be activated by structurally diverse synthetic and naturally-occurring chemicals. Although a significant amount of information is available with respect to the planar aromatic hydrocarbon AhR ligands, the actual spectrum of chemicals that can bind to and activate the AhR is only now being elucidated. In addition, the lack of information regarding the actual three-dimensional structure of the AhR ligand binding domain (LBD) has hindered detailed analysis of the molecular mechanisms by which these ligands bind to and active AhR signal transduction. In this review we describe the current state of knowledge with respect to naturally occurring AhR ligands and present and discuss the first theoretical model of the AhR LBD based on crystal structures of homologous PAS family members.

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“This receptor is typically, but not exclusively, activated by planar, polycyclic and aromatic compounds including polyaromatic hydrocarbons (PAHs), dioxins, and polychlorinated biphenyls (PCBs) (Denison et al., 2002).”
Background
Polychlorinated biphenyls, polybrominated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans
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“…and their structure–toxicity relationships, which supports the idea that the AhR is involved in the mediation of responses induced by TCCD and related PCDD, PCDF, and PCB congeners (Okey et al., 1994; Hahn, 1998, 2002; Safe, 1998; Denison et al., 2002; Denison and Nagy, 2003; Mandal, 2005).”
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“The structure of the AhR is unknown, although it has recently been modelled using a fairly remote homology [4].”
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“Because many compounds produce AhR-independent toxic and biological responses and many AhR active chemicals have not been assigned TEFs (Denison et al., 2002), there is an urgent need to evaluate which clean-up should be used (with or without nondioxin-like compounds such as PAHs) and which compounds should be tested…”
BackgroundInfluential
Perspective on receptor-associated immune response to Candida albicans single and mixed infections: Implications for therapeutics in oropharyngeal candidiasis
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Developmental Neurotoxicity of Dioxins
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“Additionally, docking and MD simulations are being implemented to investigate the atomic-level investigation of the receptor-ligand interaction and structural dynamicity of the receptor-ligand complex respectively [15, 44, 77].”
Aryl hydrocarbon receptor-induced activation of AIM2 inflammasome is mediated by MOMP and MPT: A vital therapeutic pathway for inflammation
Chen, M., Liang, Z., Sun, M., Chen, Z., Peng, C., Khan, S., Abbas, M., Chen, D., & Xie, S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116673 · Cited by 2
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Transcript variations, phylogenetic tree and chromosomal localization of porcine aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) genes
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“…relationships, which supports the idea that the AhR is involved in the mediation of responses induced by the wileyonlinelibrary.com/ETC TCDD-like polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran, and PCB congeners (Denison et al. 2002; Denison and Nagy 2003; Mandal 2005).”
BackgroundInfluential

Authors: Denison, M. S., Pandini, A., Nagy, S. R., Baldwin, E. P., & Bonati, L.
Affiliations: University of California, Davis (US)
University of Milano-Bicocca (IT)
Corresponding author: Denison, Michael S
ORCID: Denison, Michael S
Pandini, Alessandro
Baldwin, Enoch P
Bonati, Laura
Venue: Chemico-Biological Interactions
Publisher: Elsevier BV
Published: 2002-09
Volume: 141
Issue: 1-2
Pages: 3-24
ISSN: 0009-2797 (ISSN-L)
DOI: 10.1016/s0009-2797(02)00063-7
OpenAlex: W1985754063
Cited by: 485
References: 153
Citations by year: 2026: 7 · 2025: 8 · 2024: 12 · 2023: 16 · 2022: 18 · 2021: 7 · 2020: 18 · 2019: 13 · 2018: 18 · 2017: 18 · 2016: 20 · 2015: 16 · 2014: 30 · 2013: 24 · 2012: 30
FWCI: 15.36
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Chemico-Biological Interactions (publishedVersion)
PubMed (publishedVersion)
BOA (University of Milano-Bicocca) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (5r01es007072-04)
National Institute of Environmental Health Sciences (ES07059, ES 07685, R01ES007685, ES-07072, ES5707, T32ES007059)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: aryl hydrocarbon receptor, ligand binding, receptor activation, ligand-binding domain, aromatic hydrocarbons, crystal structure, signal transduction, transcription factors
MeSH terms: Animals, Binding Sites, Humans, Ligands, Protein Binding, Protein Conformation, Signal Transduction, Receptors, Aryl Hydrocarbon

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