9u80 | pdb_00009u80

Cryo-EM structure of conivaptan-bound human vasopressin V2 receptor complex with Fab

spinqualitylabelsall models 9u80, resolution 2.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9u80 is a 3 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.94Å Ligands: A1ECE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease V2R_HUMAN Nephrogenic syndrome of inappropriate antidiuresis;Inappropriate antidiuretic hormone secretion syndrome;Nephrogenic diabetes insipidus. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function C562_ECOLX Electron-transport protein of unknown function.V2R_HUMAN Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption. Publication Abstract from PubMed The vasopressin V2 receptor (V2R), a class A G protein-coupled receptor, is essential for regulating body water homeostasis. V2R antagonists have emerged as promising treatments for hyponatremia; however, the absence of structural information for antagonist-bound V2R hampers our understanding of antagonist recognition and the targeted design of V2R antagonists. In this study, we present two cryo-electron microscopy structures of inactive V2R bound to the clinically approved antagonists tolvaptan and conivaptan. Combined with functional analyses and molecular dynamic simulations, these structures reveal distinct binding poses: tolvaptan is deeply inserted within the binding pocket, whereas conivaptan is positioned at a shallower depth. Integrated analyses further define critical pharmacophoric features governing antagonist activity and unveil a TM7 helical conformation-dependent antagonism mechanism that is distinct from classical GPCR inactivation modes. Our findings deepen understanding of antagonist recognition and antagonism of V2R, providing a foundation for the development of V2R-targeted therapies. Structural insights into antagonist recognition by the vasopressin V2 receptor.,Zhang T, Liu H, You C, Zhang Y, Xu Y, Pan B, Wu C, Jin S, Yin YL, Wu K, Chen Y, Sun H, Si Y, Tan Y, Yin W, Xu HE, Guo D, Jiang Y Nat Commun. 2025 Nov 4;16(1):9734. doi: 10.1038/s41467-025-64735-x. PMID:41188237 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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