Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1992407 | The Journal of Steroid Biochemistry and Molecular Biology | 2010 | 4 Pages |
Abstract
In the nuclear receptor of vitamin D (VDR) histidine 305 participates to the anchoring of the ligand. The VDR H305Q mutation was identified in a patient who exhibited the hereditary vitamin D-resistant rickets (HVDRR). We report the crystal structure of human VDR H305Q-ligand binding domain bound to 1α,25(OH)2D3 solved at 1.8 Å resolution. The protein adopts the active conformation of the wild-type liganded VDR. A local conformational flexibility at the mutation site weakens the hydrogen bond between the 25-OH with Gln305, thus explaining the lower affinity of the mutant proteins for calcitriol. The structure provides the basis for a rational approach to the design of more potent ligands for the treatment of HVDRR.
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Authors
Natacha Rochel, Shinji Hourai, Dino Moras,