5MX7

1a,20S-dihydroxyvitamin D3 VDR complex

This is a non-PDB format compatible entry.

Summary for 5MX7

• Entry DOI: 10.2210/pdb5mx7/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, 1a,20S-dihydroxyvitamin D3, ... (4 entities in total)
• Functional Keywords: vitamin d receptor, agonist, transcription
• Biological source: Danio rerio (Zebrafish); More
• Cellular location: Nucleus : Q9PTN2 Q15788
• Total number of polymer chains: 2
• Total formula weight: 36109.25

Authors

Rochel, N.,Belorusova, A.Y. (deposition date: 2017-01-21, release date: 2017-11-29, Last modification date: 2024-01-17)

Primary citation

Lin, Z.,Chen, H.,Belorusova, A.Y.,Bollinger, J.C.,Tang, E.K.Y.,Janjetovic, Z.,Kim, T.K.,Wu, Z.,Miller, D.D.,Slominski, A.T.,Postlethwaite, A.E.,Tuckey, R.C.,Rochel, N.,Li, W.
1 alpha,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structure and Route of Chemical Synthesis.
Sci Rep, 7:10193-10193, 2017

PubMed Abstract: 1α,20S-Dihydroxyvitamin D3 [1,20S(OH)D], a natural and bioactive vitamin D3 metabolite, was chemically synthesized for the first time. X-ray crystallography analysis of intermediate 15 confirmed its 1α-OH configuration. 1,20S(OH)D interacts with the vitamin D receptor (VDR), with similar potency to its native ligand, 1α,25-dihydroxyvitamin D [1,25(OH)D] as illustrated by its ability to stimulate translocation of the VDR to the nucleus, stimulate VDRE-reporter activity, regulate VDR downstream genes (VDR, CYP24A1, TRPV6 and CYP27B1), and inhibit the production of inflammatory markers (IFNγ and IL1β). However, their co-crystal structures revealed differential molecular interactions of the 20S-OH moiety and the 25-OH moiety to the VDR, which may explain some differences in their biological activities. Furthermore, this study provides a synthetic route for the synthesis of 1,20S(OH)D using the intermediate 1α,3β-diacetoxypregn-5-en-20-one (3), and provides a molecular and biological basis for the development of 1,20S(OH)D and its analogs as potential therapeutic agents.

PubMed: 28860545
DOI: 10.1038/s41598-017-10917-7

Experimental method

X-RAY DIFFRACTION (1.98 Å)