5zwe

Covalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having a vinyl ketone group via conjugate addition reactionCovalent bond formation between histidine of Vitamin D receptor (VDR) and a full agonist having a vinyl ketone group via conjugate addition reaction

Structural highlights 5zwe is a 2 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Gene: Vdr, Nr1i1 (Buffalo rat) 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 designed and synthesized vitamin D analogues with an electrophile as covalent modifiers for the vitamin D receptor (VDR). Novel vitamin D analogues 1-4 have an electrophilic enone group at the side chain for conjugate addition to His301 or His393 in the VDR. All compounds showed specific VDR-binding potency and agonistic activity. Covalent bond formations of 1-4 with the ligand-binding domain (LBD) of VDR were evaluated by electrospray ionization mass spectrometry. All compounds were shown to covalently bind to the VDR-LBD, and the abundance of VDR-LBD corresponding conjugate adducts of 1-4 increased with incubation time. Enone compounds 1 and 2 showed higher reactivity than the ene-ynone 3 and dienone 4 compounds. Furthermore, we successfully obtained cocrystals of VDR-LBD with analogues 1-4. X-ray crystallographic analysis showed a covalent bond with His301 in VDR-LBD. We successfully synthesized vitamin D analogues that form a covalent bond with VDR-LBD. Identification of the Histidine Residue in Vitamin D Receptor That Covalently Binds to Electrophilic Ligands.,Yoshizawa M, Itoh T, Hori T, Kato A, Anami Y, Yoshimoto N, Yamamoto K J Med Chem. 2018 Jul 11. doi: 10.1021/acs.jmedchem.8b00774. PMID:29936834 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5zwe, resolution 2.72Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image