Number of the records: 1
Unique and Common Agonists Act the Insect Juvenile Hormone Rece and the Human AHR
- 1.
SYSNO ASEP 0603119 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Unique and Common Agonists Act the Insect Juvenile Hormone Rece and the Human AHR Author(s) Sedlák, David (UMG-J) RID
Tůma, R. (CZ)
Kolla, Jayaprakash Narayana (UMG-J)
Mokhamatam, Raveendra Babu (UMG-J)
Bahrová, Liliia (UMG-J)
Lisová, Michaela (UMG-J)
Bittová, Lenka (BC-A) RID, ORCID
Jindra, Marek (BC-A) RID, ORCIDNumber of authors 8 Article number 168883 Source Title Journal of Molecular Biology. - : Elsevier - ISSN 0022-2836
Roč. 437, č. 2 (2025)Number of pages 19 s. Language eng - English Country NL - Netherlands Keywords aryl-hydrocarbon receptor ; molecular-dynamics ; nuclear receptors ; protein ; modulation ; activation ; disruptors ; tryptophan ; endocrine ; homology OECD category Biochemistry and molecular biology R&D Projects GX20-05151X GA ČR - Czech Science Foundation (CSF) LM2018130 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 ; BC-A - RVO:60077344 UT WOS 001375189500001 EID SCOPUS 85211020814 DOI https://doi.org/10.1016/j.jmb.2024.168883 Annotation Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the fly Drosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes. Whilst GCE/MET and AHR are phylogenetically heterologous, their mode of action is similar. JHR is targeted by several synthetic agonists that serve as insecticides disrupting the insect endocrine system. AHR is an important regulator of human endocrine homeostasis, and it responds to environmental pollutants and endocrine disruptors. Whether AHR signaling is affected by compounds that can activate JHR has not been reported. To address this question, we screened a chemical library of 50,000 compounds to identify 93 novel JHR agonists in a reporter system based on Drosophila cells. Of these compounds, 26% modulated AHR signaling in an analogous reporter assay in a human cell line, indicating a significant overlap in the agonist repertoires of the two receptors. To explore the structural features of agonist-dependent activation of JHR and AHR, we compared the ligand-binding cavities and their interactions with selective and common ligands of AHR and GCE. Molecular dynamics modeling revealed ligand-specific as well as conserved side chains within the respective cavities. Significance of predicted interactions was supported through site-directed mutagenesis. The results have indicated that (c) 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2026 Electronic address https://www.sciencedirect.com/science/article/abs/pii/S0022283624005138?via%3Dihub
Number of the records: 1