Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor; the AhR Per-AhR/Arnt-Sim (PAS) domain binds ligands. We developed homology models of the AhR PAS domain to characterize previously observed intra- and interspecies differences in ligand binding using molecular docking. In silico structure-based virtual ligand screening using our model resulted in the identification of pinocembrin and 5-hydroxy-7-methoxyflavone, which promoted nuclear translocation and transcriptional activation of AhR and AhR-dependent induction of endogenous target genes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Nucleus / metabolism
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Drug Evaluation, Preclinical
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Humans
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Ligands
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Mice
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Models, Molecular*
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Molecular Sequence Data
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Phylogeny
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Protein Conformation
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Protein Structure, Tertiary
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Protein Transport
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Receptors, Aryl Hydrocarbon / chemistry*
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism*
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Transcriptional Activation / drug effects
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User-Computer Interface
Substances
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Ligands
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Receptors, Aryl Hydrocarbon