9w33: Difference between revisions

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'''Unreleased structure'''


The entry 9w33 is ON HOLD  until Paper Publication
==S5A1-bound inactive SSTR5 structure==
<StructureSection load='9w33' size='340' side='right'caption='[[9w33]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9w33]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=9W33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9W33 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]] 2.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EVQ:4-[8-[(2-cyclopropyl-5-ethoxy-4-methyl-phenyl)methyl]-2-oxidanylidene-1,3,8-triazaspiro[4.5]decan-3-yl]benzoic+acid'>A1EVQ</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=9w33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9w33 OCA], [https://pdbe.org/9w33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9w33 RCSB], [https://www.ebi.ac.uk/pdbsum/9w33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9w33 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/SSR5_HUMAN SSR5_HUMAN] Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization.<ref>PMID:12072395</ref> <ref>PMID:7908405</ref> <ref>PMID:8078491</ref> <ref>PMID:8373420</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The somatostatin receptor subtype 5 (SSTR5) is a critical pharmacological target involved in neuroendocrine signaling, metabolic regulation, and tumorigenesis. Despite its therapeutic potential, the structural mechanisms underlying SSTR5 inhibition by nonpeptide antagonists remain largely unresolved. In this study, we present high-resolution cryoelectron microscopy structures of human SSTR5 in complex with two selective small-molecule antagonists, antagonist 1 and S5A1, revealing the receptor's inactive conformation. Both antagonists induce a unique remodeling of extracellular loop 2, which adopts a capping architecture that sterically occludes the orthosteric site, thus preventing agonist access and stabilizing receptor inactivation. Structural analyses and functional experiments elucidate how distinct molecular moieties of the antagonists differentially contribute to inhibitory efficacy, and subtype selectivity. Furthermore, we delineate rational avenues for molecular optimization to enhance therapeutic index and mitigate off-target liabilities. These findings, complementing our previous agonist-bound structures, establish a comprehensive structural foundation for developing improved nonpeptidic SSTR5 antagonists with potential therapeutic applications for type 2 diabetes and related endocrine disorders.


Authors:  
Structural insights into nonpeptide antagonist inhibition of somatostatin receptor subtype 5.,Li Y, Xing Z, Hu W, Wu K, Xu HE, Zhao LH Proc Natl Acad Sci U S A. 2025 Dec 23;122(51):e2522515122. doi: , 10.1073/pnas.2522515122. Epub 2025 Dec 19. PMID:41417603<ref>PMID:41417603</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9w33" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li Y]]
[[Category: Xing Z]]
[[Category: Xu HE]]
[[Category: Zhao L]]
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