Belorusova Anna Y, Rochel Natacha
Department of Integrative Structural Biology, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Institut National de Sante et de Recherche Medicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Universite de Strasbourg, 67404 Illkirch, France.
Curr Top Med Chem. 2014;14(21):2368-77. doi: 10.2174/1568026615666141208095937.
The vitamin D nuclear receptor (VDR) and its ligand, 1α, 25-dihydroxyvitamin D3 (1,25(OH)2D3, or calcitriol) regulate numerous biological functions. Therefore, VDR represents an important therapeutic target in the treatment of various diseases such as cancers, psoriasis, rickets, renal osteodystrophy, and autoimmune dysfunctions. Despite the number of newly synthesized 1,25(OH)2D3 analogues, the need for highly potential modulators of VDR with precise cell-, gene- or coregulator-selectivity still exists. The information coming from the analysis of crystal structures of VDR-ligand complexes remains one of the most powerful tools to explain and validate the properties of the compounds and, furthermore, to gain new rationales for their modification. The number of reports on VDR-ligand recognition is constantly rising, and herein we review the recently published structural data. With the emphasis on the most promising compounds, such as secosteroidal compounds and 1,25(OH)2D3 mimics, we also highlight other natural ligands for VDR, evidence for the existence of an alternative ligand binding site within LBP, and identification of novel VDR modulators.
维生素D核受体（VDR）及其配体1α，25 - 二羟基维生素D3（1,25(OH)2D3，即骨化三醇）调节多种生物学功能。因此，VDR是治疗各种疾病（如癌症、银屑病、佝偻病、肾性骨营养不良和自身免疫功能障碍）的重要治疗靶点。尽管新合成了许多1,25(OH)2D3类似物，但仍需要具有精确的细胞、基因或共调节因子选择性的高潜力VDR调节剂。来自VDR - 配体复合物晶体结构分析的信息仍然是解释和验证化合物性质的最有力工具之一，此外，还能为其修饰提供新的理论依据。关于VDR - 配体识别的报道数量不断增加，在此我们综述最近发表的结构数据。重点关注最有前景的化合物，如甾体类化合物和1,25(OH)2D3模拟物，我们还强调了VDR的其他天然配体、LBP内存在替代配体结合位点的证据以及新型VDR调节剂的鉴定。
