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

被引：118

作者：

Bisson, William H. ^{[1
,2
]}

Koch, Daniel C. ^{[1
,2
]}

O'Donnell, Edmond F. ^{[1
,2
]}

Khalil, Sammy M. ^{[1
,2
]}

Kerkvliet, Nancy I. ^{[2
]}

Tanguay, Robert L. ^{[2
]}

Abagyan, Ruben ^{[3
]}

Kolluri, Siva Kumar ^{[1
,2
]}

机构：

[1] Oregon State Univ, Ctr Biol Lab, Corvallis, OR 97331 USA

[2] Oregon State Univ, Environm Hlth Sci Ctr, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA

[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 18期

关键词：

DIOXIN RECEPTOR; IDENTIFICATION; ACTIVATION; INDUCTION; PEPTIDES; PROTEINS; FLAVONES; DOCKING; COMPLEX; ENERGY;

D O I：

10.1021/jm900199u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：5635 / 5641

页数：7

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