View source for 8xve


==Cryo-EM structure of ETBR bound with BQ3020==
<StructureSection load='8xve' size='340' side='right'caption='[[8xve]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8xve]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8XVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XVE 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]] 3&#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=8xve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xve OCA], [https://pdbe.org/8xve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xve RCSB], [https://www.ebi.ac.uk/pdbsum/8xve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xve ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Endothelins and their receptors, ET(A) and ET(B), play vital roles in maintaining vascular homeostasis. Therapeutically targeting endothelin receptors, particularly through ET(A) antagonists, has shown efficacy in treating pulmonary arterial hypertension (PAH) and other cardiovascular- and renal-related diseases. Here we present cryo-electron microscopy structures of ET(A) in complex with two PAH drugs, macitentan and ambrisentan, along with zibotentan, a selective ET(A) antagonist, respectively. Notably, a specialized anti-ET(A) antibody facilitated the structural elucidation. These structures, together with the active-state structures of ET-1-bound ET(A) and ET(B), and the agonist BQ3020-bound ET(B), in complex with G(q), unveil the molecular basis of agonist/antagonist binding modes in endothelin receptors. Key residues that confer antagonist selectivity to endothelin receptors were identified along with the activation mechanism of ET(A). Furthermore, our results suggest that ECL2 in ET(A) can serve as an epitope for antibody-mediated receptor antagonism. Collectively, these insights establish a robust theoretical framework for the rational design of small-molecule drugs and antibodies with selective activity against endothelin receptors.

Structural basis of antagonist selectivity in endothelin receptors.,Hou J, Liu S, Zhang X, Tu G, Wu L, Zhang Y, Yang H, Li X, Liu J, Jiang L, Tan Q, Bai F, Liu Z, Miao C, Hua T, Luo Z Cell Discov. 2024 Jul 30;10(1):79. doi: 10.1038/s41421-024-00705-9. PMID:39075075<ref>PMID:39075075</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8xve" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Hou JY]]
[[Category: Hua T]]
[[Category: Liu SH]]
[[Category: Liu ZJ]]
[[Category: Wu LJ]]