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==CryoEM structure of Gq-coupled MRGPRD with a new agonist EP-3945==
<StructureSection load='9dqj' size='340' side='right'caption='[[9dqj]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dqj]] 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=9DQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DQJ 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BEQ:2-({1-[1-(4-methoxyphenyl)cyclopropane-1-carbonyl]piperidin-4-yl}amino)quinazolin-4(3H)-one'>A1BEQ</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=9dqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dqj OCA], [https://pdbe.org/9dqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dqj RCSB], [https://www.ebi.ac.uk/pdbsum/9dqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dqj 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 ==
The human MRGPRD protein is a member of the Mas-related G protein-coupled receptors (MRGPRs) that is involved in the sensing of pain, itch, and other inflammatory stimuli. As with other MRGPRs, MRGPRD is a relatively understudied receptor with few known agonists. The most potent small-molecule agonist of MRGPRD reported so far is beta-alanine, with an affinity in the micromole range, which largely restricts its functional study. Here, we report two MRGPRD agonists, EP-2825 and EP-3945, that are approximately 100-fold more potent than beta-alanine and determine the structures of MRGPRD-Gq in complex with EP-2825 and EP-3945, respectively. The structures reveal distinct agonist binding modes of MRGPRD and large conformational plasticity of the orthosteric pocket. Collectively, the discovery of high-affinity MRGPRD agonists and their distinct binding modes will facilitate the functional study and the structure-based design of ligands targeting this understudied receptor.

High-affinity agonists reveal recognition motifs for the MRGPRD GPCR.,Wang C, Liu Y, Lanier M, Yeager A, Singh I, Gumpper RH, Krumm BE, DeLeon C, Zhang S, Boehm M, Pittner R, Baron A, Dvorak L, Bacon C, Shoichet BK, Martinborough E, Fay JF, Cao C, Roth BL Cell Rep. 2024 Nov 23;43(12):114942. doi: 10.1016/j.celrep.2024.114942. PMID:39580805<ref>PMID:39580805</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dqj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cao C]]
[[Category: Fay JF]]
[[Category: Liu Y]]
[[Category: Roth BL]]
[[Category: Wang C]]