View source for 9hb3


==cryo-EM structure of inactive human arginine-vasopressin (AVP) V2 receptor (V2R) with Mambaquaretin1 K39A (MQK39A)==
<StructureSection load='9hb3' size='340' side='right'caption='[[9hb3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hb3]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Dendroaspis_angusticeps Dendroaspis angusticeps] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HB3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9hb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hb3 OCA], [https://pdbe.org/9hb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hb3 RCSB], [https://www.ebi.ac.uk/pdbsum/9hb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hb3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAMB1_DENAN 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).<ref>PMID:28630289</ref> <ref>PMID:33052234</ref> <ref>PMID:35122240</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dendroaspis angusticeps]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bous J]]
[[Category: Couvineau P]]
[[Category: Fouillen A]]
[[Category: Gilles N]]
[[Category: Granier S]]
[[Category: Mary C]]
[[Category: Mendre C]]
[[Category: Mouillac B]]
[[Category: Orcel H]]
[[Category: Schulte G]]