Differences in Activation of Aryl Hydrocarbon Receptors of White Sturgeon Relative to Lake Sturgeon Are Predicted by Identities of Key Amino Acids in the Ligand Binding Domain

2015 ◽  
Vol 49 (7) ◽  
pp. 4681-4689 ◽  
Author(s):  
Jon A. Doering ◽  
Reza Farmahin ◽  
Steve Wiseman ◽  
Shawn C. Beitel ◽  
Sean W. Kennedy ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Lake Sturgeon ◽  
White Sturgeon ◽  
Aryl Hydrocarbon Receptors ◽  
Aryl Hydrocarbon

scholarly journals Amino acids 3-13 and amino acids in and flanking the 23 FxxLF27 motif modulate the interaction between the N-terminal and ligand-binding domain of the androgen receptor

2002 ◽  
Vol 269 (23) ◽  
pp. 5780-5791 ◽  
Author(s):  
Karine Steketee ◽  
Cor A Berrevoets ◽  
Hendrikus J. Dubbink ◽  
Paul Doesburg ◽  
Remko Hersmus ◽  
...  
Keyword(s):  
Amino Acids ◽  
Androgen Receptor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain

scholarly journals The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing.

1995 ◽  
Vol 15 (1) ◽  
pp. 76-86 ◽  
Author(s):  
A Baniahmad ◽  
X Leng ◽  
T P Burris ◽  
S Y Tsai ◽  
M J Tsai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Activation Domain ◽  
C Terminus

The C terminus of nuclear hormone receptors is a complex structure that contains multiple functions. We are interested in the mechanism by which thyroid hormone converts its receptor from a transcriptional silencer to an activator of transcription. Both regulatory functions are localized in the ligand binding domain of this receptor superfamily member. In this study, we have identified and characterized several functional domains within the ligand binding domain of the human thyroid hormone receptor (TR beta) conferring transactivation. Interestingly, these domains are localized adjacent to hormone binding sites. One activation domain, designated tau 4, is only 17 amino acids in length and is localized at the extreme C terminus of TR. Deletion of six amino acids of tau 4 resulted in a receptor that could still bind hormone but acted as a constitutive silencer, indicating that tau 4 is required for both transactivation and relief of the silencing functions. In addition, we performed in vivo competition experiments, the results of which suggest that in the absence of tau 4 or hormone, TR is bound by a corepressor protein(s) and that one role of hormone is to release corepressor from the receptor. We propose a general model in which the role of hormone is to induce a conformational change in the receptor that subsequently affects the action of tau 4, leading to both relief of silencing and transcriptional activation.

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

scholarly journals Identification of flavone and its derivatives as potential inhibitors of transcriptional regulator LasR of Pseudomonas aeruginosa using virtual screening

2019 ◽  
Author(s):  
Narek Abelyan ◽  
Hovakim Grabski ◽  
Susanna Tiratsuyan
Keyword(s):  
Amino Acids ◽  
Virtual Screening ◽  
Quorum Sensing ◽  
Ligand Binding ◽  
Transcriptional Regulator ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Potential Inhibitors

AbstractAntibiotic resistance is a global problem nowadays and in 2017 the World Health Organization published the list of bacteria for which treatment are urgently needed, where Pseudomonas aeruginosa is of critical priority. Current therapies lack efficacy because this organism creates biofilms conferring increased resistance to antibiotics and host immune responses. The strategy is to “not kill, but disarm” the pathogen and resistance will be developed slowly. It has been shown that LasI/LasR system is the main component of the quorum sensing system in P. aeruginosa. LasR is activated by the interaction with its native autoinducer. A lot flavones and their derivatives are used as antibacterial drug compounds. The purpose is to search compounds that will inhibit LasR. This leads to the inhibition of the synthesis of virulence factors thus the bacteria will be vulnerable and not virulent. We performed virtual screening using multiple docking programs for obtaining consensus predictions. The results of virtual screening suggest benzamides which are synthetical derivatives of flavones as potential inhibitors of transcriptional regulator LasR. These are consistent with recently published experimental data, which demonstrate the high antibacterial activity of benzamides. The compounds interact with the ligand binding domain of LasR with higher binding affinity than with DNA binding domain. Among the selected compounds, by conformational analysis, it was found that there are compounds that bind to the same amino acids of ligand binding domain as the native autoinducer. This could indicate the possibility of competitive interaction of these compounds. A number of compounds that bind to other conservative amino acids ligand binding domain have also been discovered, which will be of interest for further study. Selected compounds meet the criteria necessary for their consideration as drugs and can serve as a basis for conducting further in vitro / in vivo experiments. It could be used for the development of modern anti-infective therapy based on the quorum sensing system of P. aeruginosa.HighlightsVirtual screening using multiple docking programs for consensus predictions.Virtual screening reveal benzamides as potential inhibitors of LasR.Selected compounds bind to the same amino acids of LBD as the native autoinducer.Selected compounds meet the criteria necessary for their consideration as drugs.GRAPHICAL ABSTRACT1: N- (1,3-benzodioxol-5-ylmethyl) -4- (6,8-dimethyl-4-oxochromen-2-yl) benzamide docking with LBD of LasR, A — ligand conformation predicted by AutoDock, B - by rDock and C - by LeDock,D - binding of CID 108754330 with LBD of LasR predicted by rDock.2: Four types of P. aeruginosa quorum sensing signaling systems I. Las, II. Rhl, III. Pqs and IV. IQS.

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