Modeling of the Aryl Hydrocarbon Receptor (AhR) Ligand Binding Domain and Its Utility in Virtual Ligand Screening to Predict New AhR Ligands

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• 作者：William H. Bisson ; Daniel C. Koch ; Edmond F. O’ ; Donnell ; Sammy M. Khalil ; Nancy I. Kerkvliet ; Robert L. Tanguay ; Ruben Abagyan ; Siva Kumar Kolluri
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 24, 2009
• 年：2009
• 卷：52
• 期：18
• 页码：5635-5641
• 全文大小：1014K
• 年卷期：v.52,no.18(September 24, 2009)
• ISSN：1520-4804

文摘

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.