8x7a: Difference between revisions
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==Treprostinil bound Prostacyclin Receptor G protein complex== | |||
<StructureSection load='8x7a' size='340' side='right'caption='[[8x7a]], [[Resolution|resolution]] 2.56Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8x7a]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8X7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8X7A 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]] 2.56Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y9J:2-[[(1~{R},2~{R},3~{a}~{S},9~{a}~{S})-2-oxidanyl-1-[(3~{S})-3-oxidanyloctyl]-2,3,3~{a},4,9,9~{a}-hexahydro-1~{H}-cyclopenta[g]naphthalen-5-yl]oxy]ethanoic+acid'>Y9J</scene></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=8x7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8x7a OCA], [https://pdbe.org/8x7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8x7a RCSB], [https://www.ebi.ac.uk/pdbsum/8x7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8x7a ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The prostacyclin (PGI(2)) receptor (IP) is a G(s)-coupled receptor associated with blood pressure regulation, allergy, and inflammatory response. It is a main therapeutic target for pulmonary arterial hypertension (PAH) and several other diseases. Here we report cryo-electron microscopy (cryo-EM) structures of the human IP-G(s) complex bound with two anti-PAH drugs, treprostinil and MRE-269 (active form of selexipag), at global resolutions of 2.56 and 2.41 angstrom, respectively. These structures revealed distinct features governing IP ligand binding, receptor activation, and G protein coupling. Moreover, comparison of the activated IP structures uncovered the mechanism and key residues that determine the superior selectivity of MRE-269 over treprostinil. Combined with molecular docking and functional studies, our structures provide insight into agonist selectivity, ligand recognition, receptor activation, and G protein coupling. Our results provide a structural template for further improving IP-targeting drugs to reduce off-target activation of prostanoid receptors and adverse effects. | |||
Molecular recognition and activation of the prostacyclin receptor by anti-pulmonary arterial hypertension drugs.,Wang JJ, Jin S, Zhang H, Xu Y, Hu W, Jiang Y, Chen C, Wang DW, Xu HE, Wu C Sci Adv. 2024 Feb 9;10(6):eadk5184. doi: 10.1126/sciadv.adk5184. Epub 2024 Feb 9. PMID:38335293<ref>PMID:38335293</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8x7a" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen C]] | |||
[[Category: Hu W]] | |||
[[Category: Jiang Y]] | |||
[[Category: Jin S]] | |||
[[Category: Wang DW]] | |||
[[Category: Wang JJ]] | |||
[[Category: Wu C]] | |||
[[Category: Xu HE]] | |||
[[Category: Xu Y]] | |||
[[Category: Zhang H]] | |||
