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 language | English (US) |
|---|---|
| Pages (from-to) | 3270-3279 |
| Number of pages | 10 |
| Journal | FEBS Letters |
| Volume | 590 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 1 2016 |
| Externally published | Yes |
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Keywords
- crystal structure
- vitamin D lactam derivative
- vitamin D receptor
ASJC Scopus subject areas
- Structural Biology
- Biophysics
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
Cite this
Regulation of the vitamin D receptor by vitamin D lactam derivatives. / Asano, Lisa; Waku, Tsuyoshi; Abe, Rumi; Kuwabara, Naoyuki; Ito, Ichiaki; Yanagisawa, Junn; Nagasawa, Kazuo; Shimizu, Toshiyuki.
In: FEBS Letters, Vol. 590, No. 18, 01.09.2016, p. 3270-3279.Research output: Contribution to journal › Letter
}
TY - JOUR
T1 - Regulation of the vitamin D receptor by vitamin D lactam derivatives
AU - Asano, Lisa
AU - Waku, Tsuyoshi
AU - Abe, Rumi
AU - Kuwabara, Naoyuki
AU - Ito, Ichiaki
AU - Yanagisawa, Junn
AU - Nagasawa, Kazuo
AU - Shimizu, Toshiyuki
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - crystal structure
KW - vitamin D lactam derivative
KW - vitamin D receptor
UR - http://www.scopus.com/inward/record.url?scp=84983520425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983520425&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.12348
DO - 10.1002/1873-3468.12348
M3 - Letter
C2 - 27500498
AN - SCOPUS:84983520425
VL - 590
SP - 3270
EP - 3279
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 18
ER -