3vjs

Vitamin D receptor complex with a carborane compoundVitamin D receptor complex with a carborane compound

Structural highlights 3vjs 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 1.93Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VDR_RAT 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. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis. Publication Abstract from PubMed We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo-dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical stability and a characteristically hydrophobic B-H surface). This carborane-based VDR ligand exhibited moderate vitamin D activity, comparable to that of the natural hormone, despite its simple and flexible structure. X-ray structure analysis provided direct evidence that the carborane cage binds to the hydrophobic surface of the ligand-binding pocket of the receptor, promoting transition to the active conformation. These results indicate that the spherical B-H surface of carborane can function efficiently as a hydrophobic anchor in binding to the receptor surface, thereby allowing induced fitting of the three essential hydroxyl groups on the alkyl chains to the appropriate positions for interaction with the VDR binding site, despite the entropic disadvantage of the flexible structure. We suggest that carborane structure is a promising option in the design of novel drug candidates. Boron cluster-based development of potent nonsecosteroidal vitamin D receptor ligands: direct observation of hydrophobic interaction between protein surface and carborane.,Fujii S, Masuno H, Taoda Y, Kano A, Wongmayura A, Nakabayashi M, Ito N, Shimizu M, Kawachi E, Hirano T, Endo Y, Tanatani A, Kagechika H J Am Chem Soc. 2011 Dec 28;133(51):20933-41. Epub 2011 Nov 30. PMID:22066785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sandbox vdr Vitamin D receptor 3D structures

spinqualitylabelsall models 3vjs, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image