Abstract
Active vitamin D, 1 α,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ] is a hormone that plays an essential role in calcium homeostasis and bone metabolism. 1,25-(OH) 2 D 3 is also involved in cell differentiation and proliferation, and immunomodulation. 1,25-(OH) 2 D 3 and its analogs exhibit these effects by binding to the vitamin D receptor which is a ligand-dependent transcription factor. The vitamin D receptor belongs to the nuclear receptor superfamily which includes receptors for steroids, retinoids and thyroid hormones. We developed various vitamin D analogs which specifically bind to the vitamin D receptor, and then we classified these analogs into agonist, a partial agonist and antagonist for the receptor by judging from their biological activities. Using crystal structural analysis and solution structural analysis we clarified the three-dimensional structure of the vitamin D receptor and interactions between vitamin D analogs and the vitamin D receptor. The results indicated that agonism, partial agonism and antagonism of the vitamin D receptor by the ligand binding were structure-biologically clarified.
