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Review

Vitamins D: Relationship between Structure and Biological Activity

1
Pharmaceutical Research Institute, 8 Rydygiera, Warsaw 01-793, Poland
2
Institute of Clinical Sciences, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 2119; https://doi.org/10.3390/ijms19072119
Received: 3 July 2018 / Revised: 17 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
The most active metabolite of vitamin D is 1α,25-dihydroxyvitamin D3, which is a central regulator of mineral homeostasis: excessive administration leads to hypercalcemia. Additionally, 1α,25-dihydroxyvitamin D3 is important to decision-making by cells, driving many cell types to growth arrest, differentiate and undergo apoptosis. 1α,25-Dihydroxyvitamin D3 regulates gene transcription by binding to a single known receptor, the vitamin D receptor. Rapid intracellular signals are also elicited in vitro by 1α,25-dihydroxyvitamin D3 that are independent of transcription. There are many aspects of the multiple actions of 1α,25-dihydroxyvitamin D3 that we do not fully understand. These include how a single receptor and provoked rapid events relate to the different actions of 1α,25-dihydroxyvitamin D3, its calcemic action per se, and whether a large number of genes are activated directly, via the vitamin D receptor, or indirectly. A strategy to resolving these issues has been to generate synthetic analogues of 1α,25-dihydroxyvitamin D3: Some of these separate the anti-proliferative and calcemic actions of the parent hormone. Crystallography is important to understanding how differences between 1α,25-dihydroxyvitamin D3- and analogue-provoked structural changes to the vitamin D receptor may underlie their different activity profiles. Current crystallographic resolution has not revealed such information. Studies of our new analogues have revealed the importance of the A-ring adopting the chair β-conformation upon interaction with the vitamin D receptor to receptor-affinity and biological activity. Vitamin D analogues are useful probes to providing a better understanding of the physiology of vitamin D. View Full-Text
Keywords: cell differentiation; vitamin D; vitamin D receptor; vitamin D analogues; crystallography cell differentiation; vitamin D; vitamin D receptor; vitamin D analogues; crystallography
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MDPI and ACS Style

Kutner, A.; Brown, G. Vitamins D: Relationship between Structure and Biological Activity. Int. J. Mol. Sci. 2018, 19, 2119. https://doi.org/10.3390/ijms19072119

AMA Style

Kutner A, Brown G. Vitamins D: Relationship between Structure and Biological Activity. International Journal of Molecular Sciences. 2018; 19(7):2119. https://doi.org/10.3390/ijms19072119

Chicago/Turabian Style

Kutner, Andrzej, and Geoffrey Brown. 2018. "Vitamins D: Relationship between Structure and Biological Activity" International Journal of Molecular Sciences 19, no. 7: 2119. https://doi.org/10.3390/ijms19072119

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