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7bns

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VDR complex with BXL-62

Structural highlights

7bns is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket.

Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants.,Belorusova AY, Rovito D, Chebaro Y, Doms S, Verlinden L, Verstuyf A, Metzger D, Rochel N, Laverny G Int J Mol Sci. 2022 Jul 30;23(15). pii: ijms23158445. doi: 10.3390/ijms23158445. PMID:35955580^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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, Rovito D, Chebaro Y, Doms S, Verlinden L, Verstuyf A, Metzger D, Rochel N, Laverny G. Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants. Int J Mol Sci. 2022 Jul 30;23(15). pii: ijms23158445. doi: 10.3390/ijms23158445. PMID:35955580 doi:http://dx.doi.org/10.3390/ijms23158445