Next Article in Journal
Functions of Rhotekin, an Effector of Rho GTPase, and Its Binding Partners in Mammals
Next Article in Special Issue
The Making of Hematopoiesis: Developmental Ancestry and Environmental Nurture
Previous Article in Journal
Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation
Previous Article in Special Issue
Molecular Regulation of Differentiation in Early B-Lymphocyte Development

Vitamins D: Relationship between Structure and Biological Activity

Pharmaceutical Research Institute, 8 Rydygiera, Warsaw 01-793, Poland
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;
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
Show Figures

Graphical abstract

MDPI and ACS Style

Kutner, A.; Brown, G. Vitamins D: Relationship between Structure and Biological Activity. Int. J. Mol. Sci. 2018, 19, 2119.

AMA Style

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

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.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop