1. Regulation of the vitamin D receptor by vitamin D lactam derivatives.
- Author
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Asano, Lisa, Waku, Tsuyoshi, Abe, Rumi, Kuwabara, Naoyuki, Ito, Ichiaki, Yanagisawa, Junn, Nagasawa, Kazuo, and Shimizu, Toshiyuki
- Subjects
VITAMIN D receptors ,VITAMIN D ,X-ray crystallography ,LIGAND binding (Biochemistry) ,GENE expression ,LACTAMS - Abstract
The active metabolite of vitamin D
3 , 1α,25-dihydroxyvitamin D3 , acts as a ligand for the vitamin D receptor ( VDR) and activates VDR-mediated gene expression. Recently, we characterized 1α,25-dihydroxyvitamin D3 -26,23-lactams ( DLAMs), which mimic vitamin D3 metabolites, as noncalcemic VDR ligands that barely activate the receptor. In this study, we present structural insights onto the regulation of VDR function by DLAMs. X-ray crystallographic analysis revealed that DLAMs induced a large conformational change in the loop region between helices H6 and H7 in the VDR ligand-binding domain. Our structural analysis suggests that targeting of the loop region may be a new mode of VDR regulation. [ABSTRACT FROM AUTHOR]- Published
- 2016
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