PUBLICATION
Structural analysis of VDR complex with ZK168281 antagonist
- Authors
- Belorusova, A., Chalhoub, S., Rovito, D., Rochel, N.
- ID
- ZDB-PUB-200814-9
- Date
- 2020
- Source
- Journal of medicinal chemistry 63(17): 9457-9463 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Protein Domains
- Cell Line
- Receptors, Calcitriol/antagonists & inhibitors*
- Receptors, Calcitriol/chemistry
- Receptors, Calcitriol/metabolism*
- Protein Binding
- Rats
- Zebrafish
- Animals
- Ligands
- Models, Molecular
- Calcitriol/analogs & derivatives*
- Calcitriol/metabolism
- Calcitriol/pharmacology
- PubMed
- 32787090 Full text @ J. Med. Chem.
Citation
Belorusova, A., Chalhoub, S., Rovito, D., Rochel, N. (2020) Structural analysis of VDR complex with ZK168281 antagonist. Journal of medicinal chemistry. 63(17):9457-9463.
Abstract
Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active confor-mation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1a,25-dihydroxyvitamin D3. Here we report the crystal structure of the zebrafish VDR ligand binding domain in complex with the ZK168281 antagonist, revealing that the ligand prevents optimal folding of the C-terminal region of VDR. This inter-ference was confirmed by HDX-MS in solution.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping