title: Structural aspects of Vitamin D endocrinology.
abstract: 1α,25-Dihydroxvitamin D3(1,25(OH)2D3) is the hormonally active form of vitamin D3. Its synthesis and its metabolites, their transport and elimination as well as action on transcriptional regulation involves the harmonic cooperation of diverse proteins with vitamin D binding capacities such as vitamin D binding protein (DBP), cytochrome P450 enzymes or the nuclear vitamin receptor (VDR). The genomic mechanism of 1,25(OH)2D3action involves its binding to VDR that functionally acts as a heterodimer with retinoid X receptor. The crystal structures of the most important proteins for vitamin D3, VDR, DBP, CYP2R1 and CYP24A1, have provided identification of mechanisms of actions of these proteins and those mediating VDR-regulated transcription. This review will present the structural information on recognition of the vitamin D3and metabolites by CYP proteins and DBP as well as the structural basis of VDR activation by 1,25(OH)2D3and metabolites. Additionally, we will describe, the implications of the VDR mutants associated with hereditary vitamin D-resistant rickets (HVDRR) that display impaired function.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de La Santé et de La Recherche Médicale (INSERM), U964/Centre National de Recherche Scientifique (CNRS), UMR7104/Université de Strasbourg, 67404 Illkirch, France. Electronic address: rochel@igbmc.fr.
authors.forename: Natacha
authors.initials: N
authors.lastname: Rochel
authors.affiliation: Institute of Biopharmacy, School of Pharmacy, Faculty of Heath Science, University of Eastern Finland, Yliopistonranta 1C, Canthia 2036, 70210 Kuopio, Finland. Electronic address: ferdinandmolnar@gmail.com.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Molnár
mesh_terms: D000494:Allosteric Regulation; D002762:Cholecalciferol / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase / Q000737:chemistry / Q000378:metabolism; D000072467:Cytochrome P450 Family 2 / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D063730:Rickets, Hypophosphatemic / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000737:chemistry / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014809:Vitamin D-Binding Protein; D002762:Cholecalciferol; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: Allostery; CYPs; DBP; HVDRR; Structure; VDR; Vitamin D3