5yc8: Difference between revisions
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==Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor bound with NMS (Hg-derivative)== | ==Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor bound with NMS (Hg-derivative)== | ||
<StructureSection load='5yc8' size='340' side='right' caption='[[5yc8]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='5yc8' size='340' side='right'caption='[[5yc8]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5yc8]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5yc8]] is a 1 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=5YC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YC8 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3C0:N-METHYL+SCOPOLAMINE'>3C0</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</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=5yc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yc8 OCA], [https://pdbe.org/5yc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yc8 RCSB], [https://www.ebi.ac.uk/pdbsum/5yc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yc8 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/ACM2_HUMAN ACM2_HUMAN] Disease susceptibility is associated with variations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[[ | [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/ACM2_HUMAN ACM2_HUMAN] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 5yc8" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5yc8" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Hirata | [[Category: Large Structures]] | ||
[[Category: Horita | [[Category: Hirata K]] | ||
[[Category: Iwata | [[Category: Horita S]] | ||
[[Category: Kinoshita | [[Category: Iwata S]] | ||
[[Category: Kobayashi | [[Category: Kinoshita M]] | ||
[[Category: Kobilka | [[Category: Kobayashi T]] | ||
[[Category: Maeda | [[Category: Kobilka BK]] | ||
[[Category: Murata | [[Category: Maeda S]] | ||
[[Category: Suno | [[Category: Murata T]] | ||
[[Category: Tawaramoto | [[Category: Suno R]] | ||
[[Category: Tsujimoto | [[Category: Tawaramoto MS]] | ||
[[Category: Yamamoto | [[Category: Tsujimoto H]] | ||
[[Category: Yamashita | [[Category: Yamamoto M]] | ||
[[Category: Yasuda | [[Category: Yamashita K]] | ||
[[Category: Yasuda S]] | |||
Latest revision as of 11:26, 22 November 2023
Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor bound with NMS (Hg-derivative)Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor bound with NMS (Hg-derivative)
Structural highlights
DiseaseACM2_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry. FunctionC562_ECOLX Electron-transport protein of unknown function.ACM2_HUMAN The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Publication Abstract from PubMedHuman muscarinic receptor M2 is one of the five subtypes of muscarinic receptors belonging to the family of G-protein-coupled receptors. Muscarinic receptors are targets for multiple neurodegenerative diseases. The challenge has been designing subtype-selective ligands against one of the five muscarinic receptors. We report high-resolution structures of a thermostabilized mutant M2 receptor bound to a subtype-selective antagonist AF-DX 384 and a nonselective antagonist NMS. The thermostabilizing mutation S110R in M2 was predicted using a theoretical strategy previously developed in our group. Comparison of the crystal structures and pharmacological properties of the M2 receptor shows that the Arg in the S110R mutant mimics the stabilizing role of the sodium cation, which is known to allosterically stabilize inactive state(s) of class A GPCRs. Molecular dynamics simulations reveal that tightening of the ligand-residue contacts in M2 receptors compared to M3 receptors leads to subtype selectivity of AF-DX 384. Structural insights into the subtype-selective antagonist binding to the M2 muscarinic receptor.,Suno R, Lee S, Maeda S, Yasuda S, Yamashita K, Hirata K, Horita S, Tawaramoto MS, Tsujimoto H, Murata T, Kinoshita M, Yamamoto M, Kobilka BK, Vaidehi N, Iwata S, Kobayashi T Nat Chem Biol. 2018 Dec;14(12):1150-1158. doi: 10.1038/s41589-018-0152-y. Epub, 2018 Nov 12. PMID:30420692[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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