9EZ2

Vitamin D receptor complex with 1,4b,25-trihydroxyvitamin D3

This is a non-PDB format compatible entry.

Summary for 9EZ2

• Entry DOI: 10.2210/pdb9ez2/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 2, 1,4b,25-trihydroxyvitamin D3, ... (5 entities in total)
• Functional Keywords: agonist, vitamin d metabolite, vdr, transcription
• Biological source: Danio rerio (zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 36132.22

Authors

Rochel, N. (deposition date: 2024-04-10, release date: 2024-06-19)

Primary citation

Peluso-Iltis, C.,Pierrat, N.,Rovito, D.,Osz, J.,Sawada, D.,Kittaka, A.,Laverny, G.,Rochel, N.
4-Hydroxy-1 alpha ,25-Dihydroxyvitamin D 3 : Synthesis and Structure-Function Study.
Biomolecules, 14:-, 2024

PubMed Abstract: The active vitamin D metabolites, 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D is a major one. This study aims to investigate the structure-activity relationships of 4-hydroxy derivatives of 1,25D. Structural analysis indicates that 1,4α,25(OH)D and 1,4β,25(OH)D maintain the anchoring hydrogen bonds of 1,25D and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D and 1,4β,25D are as potent as 1,25D in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound.

PubMed: 38785958
DOI: 10.3390/biom14050551

Experimental method

X-RAY DIFFRACTION (1.8 Å)