Regulation of the vitamin D receptor by vitamin D lactam derivatives

Lisa Asano, Tsuyoshi Waku, Rumi Abe, Naoyuki Kuwabara, Ichiaki Ito, Junn Yanagisawa, Kazuo Nagasawa, Toshiyuki Shimizu

Research output: Contribution to journalLetter

4 Scopus citations

Abstract

The active metabolite of vitamin D3, 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.

Original languageEnglish (US)
Pages (from-to)3270-3279
Number of pages10
JournalFEBS Letters
Volume590
Issue number18
DOIs
StatePublished - Sep 1 2016

Keywords

  • crystal structure
  • vitamin D lactam derivative
  • vitamin D receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Asano, L., Waku, T., Abe, R., Kuwabara, N., Ito, I., Yanagisawa, J., Nagasawa, K., & Shimizu, T. (2016). Regulation of the vitamin D receptor by vitamin D lactam derivatives. FEBS Letters, 590(18), 3270-3279. https://doi.org/10.1002/1873-3468.12348