Structural highlights
Function
VDRA_DANRE Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis.[1]
Publication Abstract from PubMed
Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1alpha,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 interference was confirmed by hydrogen-deuterium exchange mass spectrometry (HDX-MS) in solution.
Structural Analysis of VDR Complex with ZK168281 Antagonist.,Belorusova AY, Chalhoub S, Rovito D, Rochel N J Med Chem. 2020 Aug 20. doi: 10.1021/acs.jmedchem.0c00656. PMID:32787090[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ciesielski F, Rochel N, Moras D. Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42. Epub 2007 Jan 10. PMID:17218092 doi:http://dx.doi.org/10.1016/j.jsbmb.2006.12.003
- ↑ Belorusova AY, Chalhoub S, Rovito D, Rochel N. Structural Analysis of VDR Complex with ZK168281 Antagonist. J Med Chem. 2020 Sep 10;63(17):9457-9463. PMID:32787090 doi:10.1021/acs.jmedchem.0c00656
