Identification of Amino Acid Residues in the Ligand-Binding Domain of the Aryl Hydrocarbon Receptor Causing the Species-Specific Response to Omeprazole: Possible Determinants for Binding Putative Endogenous Ligands

2013 ◽  
Vol 85 (2) ◽  
pp. 279-289 ◽  
Author(s):  
Kazuhiro Shiizaki ◽  
Seiichiroh Ohsako ◽  
Masanobu Kawanishi ◽  
Takashi Yagi
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Aryl Hydrocarbon Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Specific Response ◽  
Amino Acid Residues ◽  
Endogenous Ligands ◽  
Aryl Hydrocarbon ◽  
Species Specific

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

2009 ◽  
Vol 52 (18) ◽  
pp. 5635-5641 ◽  
Author(s):  
William H. Bisson ◽  
Daniel C. Koch ◽  
Edmond F. O’Donnell ◽  
Sammy M. Khalil ◽  
Nancy I. Kerkvliet ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Aryl Hydrocarbon Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Aryl Hydrocarbon ◽  
Ligand Screening ◽  
Virtual Ligand Screening

scholarly journals An Aryl Hydrocarbon Receptor from the Caecilian Gymnopis multiplicata Suggests Low Dioxin Affinity in the Ancestor of All Three Amphibian Orders

2019 ◽  
Author(s):  
Sarah A. Kazzaz ◽  
Sara Giani Tagliabue ◽  
Diana G. Franks ◽  
Michael S. Denison ◽  
Mark E. Hahn ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Aryl Hydrocarbon Receptor ◽  
Common Ancestor ◽  
Homology Model ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Ambystoma Mexicanum ◽  
List Type ◽  
Aryl Hydrocarbon ◽  
And Function

AbstractThe aryl hydrocarbon receptor (AHR) plays pleiotropic roles in the development and physiology of vertebrates in conjunction with xenobiotic and endogenous ligands. It is best known for mediating the toxic effects of dioxin-like pollutants such as 2,3,7,8-tetracholordibenzo-p-dioxin (TCDD). While most vertebrates possess at least one AHR that binds TCDD tightly, amphibian AHRs bind TCDD with very low affinity. Previous analyses of AHRs from Xenopus laevis (a frog; order Anura) and Ambystoma mexicanum (a salamander; order Urodela) identified three amino acid residues in the ligand-binding domain (LBD) that underlie low-affinity binding. In X. laevis AHR1β, these are A354, A370, and N325. Here we extend the analysis of amphibian AHRs to the caecilian Gymnopis multiplicata, representing the remaining extant amphibian order, Apoda. G. multiplicata AHR groups with the monophyletic vertebrate AHR/AHR1 clade. The LBD includes all three signature residues of low TCDD affinity, and a structural homology model suggests that its architecture closely resembles those of other amphibians. In transactivation assays, the EC50 for reporter gene induction by TCDD was 17.17 nM, comparable to X. laevis AhR1β (26.23 nM) and Ambystoma AHR (34.09 nM) and dramatically higher than mouse AhR (0.13 nM), a trend generally reflected in direct measures of TCDD binding. These shared properties distinguish amphibian AHRs from the high-affinity proteins typical of both more ancient vertebrate groups (teleost fish) and those that appeared more recently (tetrapods). We suggest that AHRs with low TCDD affinity represent a basal characteristic that evolved in a common ancestor of all three extant amphibian groups.Research HighlightsA caecilian aryl hydrocarbon receptor exhibits low dioxin binding and sensitivity.The protein’s ligand-binding domain resembles frog and salamander AHRs in structure and function.AHR with low dioxin affinity likely evolved in a common ancestor of all three extant amphibian groups.Graphical Abstract

Sign in / Sign up

Export Citation Format

Share Document