Počet záznamů: 1
Unique and Common Agonists Act the Insect Juvenile Hormone Rece and the Human AHR
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SYSNO ASEP 0603119 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Unique and Common Agonists Act the Insect Juvenile Hormone Rece and the Human AHR Tvůrce(i) 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, ORCIDCelkový počet autorů 8 Číslo článku 168883 Zdroj.dok. Journal of Molecular Biology. - : Elsevier - ISSN 0022-2836
Roč. 437, č. 2 (2025)Poč.str. 19 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova aryl-hydrocarbon receptor ; molecular-dynamics ; nuclear receptors ; protein ; modulation ; activation ; disruptors ; tryptophan ; endocrine ; homology Obor OECD Biochemistry and molecular biology CEP GX20-05151X GA ČR - Grantová agentura ČR LM2018130 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 ; BC-A - RVO:60077344 UT WOS 001375189500001 EID SCOPUS 85211020814 DOI https://doi.org/10.1016/j.jmb.2024.168883 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2026 Elektronická adresa https://www.sciencedirect.com/science/article/abs/pii/S0022283624005138?via%3Dihub
Počet záznamů: 1