View source for 8dzs


==GR89,696 bound Kappa Opioid Receptor in complex with Gz==
<StructureSection load='8dzs' size='340' side='right'caption='[[8dzs]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dzs]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZS 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U9I:methyl+(3~{R})-4-[2-(3,4-dichlorophenyl)ethanoyl]-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate'>U9I</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=8dzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzs OCA], [https://pdbe.org/8dzs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzs RCSB], [https://www.ebi.ac.uk/pdbsum/8dzs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzs ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The kappa-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders(1). However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects(2). The initiation of KOR signalling requires the G(i/o)-family proteins including the conventional (G(i1), G(i2), G(i3), G(oA) and G(oB)) and nonconventional (G(z) and G(g)) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G(i1), G(oA), G(z) and G(g)-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing G(i/o)-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR.

Ligand and G-protein selectivity in the kappa-opioid receptor.,Han J, Zhang J, Nazarova AL, Bernhard SM, Krumm BE, Zhao L, Lam JH, Rangari VA, Majumdar S, Nichols DE, Katritch V, Yuan P, Fay JF, Che T Nature. 2023 May;617(7960):417-425. doi: 10.1038/s41586-023-06030-7. Epub 2023 , May 3. PMID:37138078<ref>PMID:37138078</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dzs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Opioid receptor|Opioid receptor]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Che T]]
[[Category: Fay JF]]