9hb3

cryo-EM structure of inactive human arginine-vasopressin (AVP) V2 receptor (V2R) with Mambaquaretin1 K39A (MQK39A)

spinqualitylabelsall models 9hb3, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9hb3 is a 5 chain structure with sequence from Dendroaspis angusticeps and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MAMB1_DENAN Selectively interacts with vasopressin V2 receptor (V2R/AVPR2) and fully inhibits three major signaling pathways of this receptor that are GalphaS protein, the interaction with beta-arrestin and activation of MAP kinase (PubMed:28630289, PubMed:35122240). Inhibits vasopressin binding human V2R in the nanomolar range (Ki=5.02 nM), and also potently inhibits vasopressin-induced cAMP production (IC(50)=94 nM) (PubMed:35122240). In vivo, this protein shows an aquaretic effect (PubMed:28630289, PubMed:35122240). Urine output increases and urine osmolality decreases dramatically under treatment with this protein, without differences observed between healthy mice and the pcy mice model of the autosomal-dominant polycystic kidney disease (ADPKD) (PubMed:28630289). This protein does not modify electrolyte, protein and urea excretions in the urine samples, but produces a 3-fold decrease of creatinine levels (PubMed:28630289). Intraperitoneal injection of this protein into the pcy mice significantly reduces the number of renal cysts and the total area of cysts (PubMed:28630289). This protein also shows high efficacy in preventing hyponatremia in rat models (induced by DAVP) (PubMed:33052234). Is highly visible in mice liver and kidney after intravenous injection (PubMed:33052234). Is rapidly eliminated in the liver, whereas it exhibits slow elimination in the kidney due to the high expression of V2R which acts as a reservoir (PubMed:33052234). In addition, its elimination from blood is rapid (PubMed:33052234). Fluorescent MQ1 probes could also be used for imaging V2R-overexpressing cancer cells; note that these probes label the three renal cancer cell lines CAKI-2, ACHN and A498 that highly express V2R (PubMed:33052234). In vivo, does not show any toxicity on animals, even at highest doses tested, such as prostration, spidy coat, appetite or weight loss (PubMed:33052234).

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