View source for 9vmo


==Cryo-EM structure of the ITA-OXGR1-Gq complex==
<StructureSection load='9vmo' size='340' side='right'caption='[[9vmo]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vmo]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VMO 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ITN:2-METHYLIDENEBUTANEDIOIC+ACID'>ITN</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=9vmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vmo OCA], [https://pdbe.org/9vmo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vmo RCSB], [https://www.ebi.ac.uk/pdbsum/9vmo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vmo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_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 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rosacea, an inflammatory skin disorder, poses a dilemma owing to limited effectiveness of treatments for pathological vasodilation-mediated erythema. Here, we identify oxoglutaric acid (alpha-KG) as a rosacea-associated metabolite elevated in patients and correlated with erythema severity. Exogenous alpha-KG administration ameliorates rosacea-like manifestations in murine models. Mechanistically, alpha-KG activates OXGR1, a vascular smooth muscle cell (VSMC)-enriched G protein-coupled receptor (GPCR) to induce Gq signaling and enhance MYL9 phosphorylation, promoting VSMC contraction and limiting vasodilation. Cryo-electron microscopy (cryo-EM) structures of OXGR1-Gq complexes bound to alpha-KG or itaconate reveal a specific bipartite-acid pocket recognizing its endogenous agonist and an activation mechanism distinct from classical GPCRs. Building on these structures, we developed A-1, a synthetic selective OXGR1 agonist that mitigates erythema and inflammation with efficacy comparable to first-line therapy while offering enhanced safety in rosacea-like models. These findings link a metabolite to vascular dysfunction and nominate OXGR1 agonism for precision treatment of erythema and vascular disorders.

Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema.,Xiao W, Zhu Y, Tang X, Zhu K, Zhang W, Chen M, Cai K, Xu S, Wu Z, Wang M, Liu J, Long L, Tan Z, Wu A, Zhou S, Zhao Z, Tang Y, Huang Y, Wang B, Liu F, Wang Q, Yang F, Jian D, Shi W, Xie H, Chen X, Guo L, Deng Z, Sun J, Li J Cell. 2026 Mar 5:S0092-8674(26)00164-9. doi: 10.1016/j.cell.2026.01.036. PMID:41791372<ref>PMID:41791372</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vmo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Deng ZL]]
[[Category: Guo LL]]
[[Category: Li J]]
[[Category: Sun JP]]
[[Category: Tang XJ]]
[[Category: Xiao WQ]]
[[Category: Zhu KK]]
[[Category: Zhu Y]]