TitleModeling of the aryl hydrocarbon receptor (AhR) ligand binding domain and its utility in virtual ligand screening to predict new AhR ligands.
Publication TypeJournal Article
Year of Publication2009
AuthorsBisson, WH, Koch, DC, O'Donnell, EF, Khalil, SM, Kerkvliet, NI, Tanguay, RL, Abagyan, R, Kolluri, SK
JournalJ Med Chem
Date Published2009 Sep 24
KeywordsAmino Acid Sequence, Animals, Cell Line, Cell Nucleus, Drug Evaluation, Preclinical, Humans, Ligands, Mice, Models, Molecular, Molecular Sequence Data, Phylogeny, Protein Conformation, Protein Structure, Tertiary, Protein Transport, Receptors, Aryl Hydrocarbon, Transcriptional Activation, User-Computer Interface

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.

Alternate JournalJ. Med. Chem.
PubMed ID19719119
PubMed Central IDPMC3289977
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES000210-38 / ES / NIEHS NIH HHS / United States
P30ES00210 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
P42 ES016465-02 / ES / NIEHS NIH HHS / United States
T32 ES007060 / ES / NIEHS NIH HHS / United States
T32 ES007060-20 / ES / NIEHS NIH HHS / United States
T32ES07060 / ES / NIEHS NIH HHS / United States