Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants.
Fiche publication
Date publication
juillet 2022
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel, Dr ROCHEL-GUIBERTEAU Natacha, Dr LAVERNY Gilles
Tous les auteurs :
Belorusova AY, Rovito D, Chebaro Y, Doms S, Verlinden L, Verstuyf A, Metzger D, Rochel N, Laverny G
Lien Pubmed
Résumé
The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket.
Mots clés
rare diseases, structure function relationship, vitamin D
Référence
Int J Mol Sci. 2022 07 30;23(15):