5mx7

1a,20S-dihydroxyvitamin D3 VDR complex1a,20S-dihydroxyvitamin D3 VDR complex

Structural highlights

5mx7 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 1.98Å
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

1alpha,20S-Dihydroxyvitamin D3 [1,20S(OH)2D3], a natural and bioactive vitamin D3 metabolite, was chemically synthesized for the first time. X-ray crystallography analysis of intermediate 15 confirmed its 1alpha-OH configuration. 1,20S(OH)2D3 interacts with the vitamin D receptor (VDR), with similar potency to its native ligand, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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 (IFNgamma and IL1beta). 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)2D3 using the intermediate 1alpha,3beta-diacetoxypregn-5-en-20-one (3), and provides a molecular and biological basis for the development of 1,20S(OH)2D3 and its analogs as potential therapeutic agents.

1alpha,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structure and Route of Chemical Synthesis.,Lin Z, Chen H, Belorusova AY, Bollinger JC, Tang EKY, Janjetovic Z, Kim TK, Wu Z, Miller DD, Slominski AT, Postlethwaite AE, Tuckey RC, Rochel N, Li W Sci Rep. 2017 Aug 31;7(1):10193. doi: 10.1038/s41598-017-10917-7. PMID:28860545^[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
↑ Lin Z, Chen H, Belorusova AY, Bollinger JC, Tang EKY, Janjetovic Z, Kim TK, Wu Z, Miller DD, Slominski AT, Postlethwaite AE, Tuckey RC, Rochel N, Li W. 1alpha,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structure and Route of Chemical Synthesis. Sci Rep. 2017 Aug 31;7(1):10193. doi: 10.1038/s41598-017-10917-7. PMID:28860545 doi:http://dx.doi.org/10.1038/s41598-017-10917-7

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OCA

[1] 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

[2] Lin Z, Chen H, Belorusova AY, Bollinger JC, Tang EKY, Janjetovic Z, Kim TK, Wu Z, Miller DD, Slominski AT, Postlethwaite AE, Tuckey RC, Rochel N, Li W. 1alpha,20S-Dihydroxyvitamin D3 Interacts with Vitamin D Receptor: Crystal Structure and Route of Chemical Synthesis. Sci Rep. 2017 Aug 31;7(1):10193. doi: 10.1038/s41598-017-10917-7. PMID:28860545 doi:http://dx.doi.org/10.1038/s41598-017-10917-7

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