8pz8

crystal structure of VDR in complex with D-Bishomo-1a,25-dihydroxyvitamin D3 Analog 54

spinqualitylabelsall models 8pz8, resolution 2.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8pz8 is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.64Å Ligands: IFU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VDRA_DANRE Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis. Publication Abstract from PubMed The biologically active metabolite of vitamin D(3) - calcitriol - is a hormone involved in the regulation of calcium-phosphate homeostasis, immunological processes and cell differentiation, being therefore essential for the proper functioning of the human body. This suggests many applications of this steroid in the treatment of diseases such as rickets, psoriasis and some cancers. Unfortunately, using therapeutic doses of calcitriol is associated with high concentrations of this compound which causes hypercalcemia. For this reason, new calcitriol analogs are constantly sought, devoid of calcemic effects but maintaining its beneficial properties. In this study, we present the synthesis of vitamin D derivatives characterized by an enlarged (seven-membered) ring D. Preparation of the designed vitamin D compounds required separate syntheses of crucial building blocks (C/D-rings fragments with side chain and rings A) which were combined by different methods, including Wittig-Horner reaction and Suzuki coupling. Biological activities of the target vitamin D analogs were assessed both in vitro and in vivo, demonstrating their significant potency compared to the natural hormone. Furthermore, the successful crystallization of these compounds with the vitamin D receptor (VDR) enabled us to investigate additional molecular interactions with this protein. Design, synthesis, and biological activity of D-bishomo-1alpha,25-dihydroxyvitamin D(3) analogs and their crystal structures with the vitamin D nuclear receptor.,Fabisiak A, Brzeminski P, Sicinski RR, Rochel N, Maj E, Filip-Psurska B, Wietrzyk J, Plum LA, DeLuca HF Eur J Med Chem. 2024 May 5;271:116403. doi: 10.1016/j.ejmech.2024.116403. Epub , 2024 Apr 10. PMID:38615411 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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