8dwh: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8dwh]] is a 4 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=8DWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DWH FirstGlance]. <br> | <table><tr><td colspan='2'>[[8dwh]] is a 4 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=8DWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DWH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U2U:N- | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U2U:~{N}-[2-(1-azanylisoquinolin-6-yl)oxy-4-methyl-phenyl]-2-methoxy-benzenesulfonamide'>U2U</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=8dwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dwh OCA], [https://pdbe.org/8dwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dwh RCSB], [https://www.ebi.ac.uk/pdbsum/8dwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dwh ProSAT]</span></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=8dwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dwh OCA], [https://pdbe.org/8dwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dwh RCSB], [https://www.ebi.ac.uk/pdbsum/8dwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dwh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | [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 MAS-related G protein-coupled receptor X1 (MRGPRX1) is preferentially expressed in the small-diameter primary sensory neurons and involved in the mediation of nociception and pruritus. Central activation of MRGPRX1 by the endogenous opioid peptide fragment BAM8-22 and its positive allosteric modulator ML382 has been shown to effectively inhibit persistent pain, making MRGPRX1 a promising target for non-opioid pain treatment. However, the activation mechanism of MRGPRX1 is still largely unknown. Here we report three high-resolution cryogenic electron microscopy structures of MRGPRX1-Galphaq in complex with BAM8-22 alone, with BAM8-22 and ML382 simultaneously as well as with a synthetic agonist compound-16. These structures reveal the agonist binding mode for MRGPRX1 and illuminate the structural requirements for positive allosteric modulation. Collectively, our findings provide a molecular understanding of the activation and allosteric modulation of the MRGPRX1 receptor, which could facilitate the structure-based design of non-opioid pain-relieving drugs. | |||
Ligand recognition and allosteric modulation of the human MRGPRX1 receptor.,Liu Y, Cao C, Huang XP, Gumpper RH, Rachman MM, Shih SL, Krumm BE, Zhang S, Shoichet BK, Fay JF, Roth BL Nat Chem Biol. 2023 Apr;19(4):416-422. doi: 10.1038/s41589-022-01173-6. Epub 2022 , Oct 27. PMID:36302898<ref>PMID:36302898</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8dwh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||