5xzf

Vitamin D receptor with a synthetic ligand ADRO1

spinqualitylabelsall models 5xzf, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xzf is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 8J0, FMT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MED1_HUMAN Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Publication Abstract from PubMed Both 25 R- and 25 S-25-adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3 (4a and 4b) were stereoselectively synthesized by a Pd(0)-catalyzed ring closure and Suzuki-Miyaura coupling between enol-triflate 7 and alkenyl-boronic ester 8. The 25 S isomer (4b) showed high vitamin D receptor (VDR) affinity (50% of that of the natural hormone 1alpha,25-dihydroxyvitamin D3, 1) and transactivation potency (kidney HEK293, 90%). In endogenous gene expression, it showed high cell-type selectivity for kidney cells (HEK293, CYP24A1 160% of 1), bone cells (MG63, osteocalcin 64%), and monocytes (U937, CAMP 96%) over intestine (SW480, CYP24A1 8%) and skin (HaCaT, CYP24A1 7%) cells. The X-ray crystal structural analysis of 4b in complex with rat VDR-ligand binding domain (LBD) showed the highest Calpha positional shift from the 1/VDR-LBD complex at helix 11. Helix 11 of the 4b and 1 VDR-LBD complexes also showed significant differences in surface properties. These results suggest that 4b should be examined further as another candidate for a mild preventive osteoporosis agent. 25 S-Adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3: Synthesis, Tissue Selective Biological Activities, and X-ray Crystal Structural Analysis of Its Vitamin D Receptor Complex.,Otero R, Ishizawa M, Numoto N, Ikura T, Ito N, Tokiwa H, Mourino A, Makishima M, Yamada S J Med Chem. 2018 Jul 23. doi: 10.1021/acs.jmedchem.8b00427. PMID:29989817 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Vitamin D receptor 3D structures

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