Muscarinic acetylcholine receptor

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spinqualitylabelsall models Human muscarinic acetylcholine receptor M2 complex with antagonist (PDB code 5zkb) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Muscarinic acetylcholine receptors (mAChR) contain 5 subtypes M1-M5. Subtypes M1,M3,M5 activate phospholipase C which leads to activation of protein kinase C. M2 and M4 inhibit adenylyl cyclase activity and activate G protein-gated potassium channels[1]. mAChRs belong to the family of rhodopsin-like G protein coupled seven transmembrane helix receptors and perform various non-neuronal functions[2]. Disease mAChR M1 agonists are developed for treatment of Alzheimer disease[3]. M2 antagonists are developed for treatment of Alzheimer disease and M3 antagonists for treatment of overactive bladder and chronic obstructive pulmonary disease[4] Structural highlights Antagonists bind to mAChR M2 at the tyrosine lid. The antagonist interacts with protein residues 107, Y104, Y403 and N404[5].

3D Structures of muscarinic acetylcholine receptors

Updated on 08-January-2020

References

1. ↑ Ishii M, Kurachi Y. Muscarinic acetylcholine receptors. Curr Pharm Des. 2006;12(28):3573-81. doi: 10.2174/138161206778522056. PMID:17073660 doi:http://dx.doi.org/10.2174/138161206778522056
2. ↑ Ockenga W, Kuhne S, Bocksberger S, Banning A, Tikkanen R. Non-neuronal functions of the m2 muscarinic acetylcholine receptor. Genes (Basel). 2013 Apr 2;4(2):171-97. doi: 10.3390/genes4020171. PMID:24705159 doi:http://dx.doi.org/10.3390/genes4020171
3. ↑ Jiang S, Li Y, Zhang C, Zhao Y, Bu G, Xu H, Zhang YW. M1 muscarinic acetylcholine receptor in Alzheimer's disease. Neurosci Bull. 2014 Apr;30(2):295-307. doi: 10.1007/s12264-013-1406-z. Epub 2014 , Mar 3. PMID:24590577 doi:http://dx.doi.org/10.1007/s12264-013-1406-z
4. ↑ Eglen RM. Muscarinic receptor subtype pharmacology and physiology. Prog Med Chem. 2005;43:105-36. doi: 10.1016/S0079-6468(05)43004-0. PMID:15850824 doi:http://dx.doi.org/10.1016/S0079-6468(05)43004-0
5. ↑ 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. Structural insights into the subtype-selective antagonist binding to the M2 muscarinic receptor. Nat Chem Biol. 2018 Dec;14(12):1150-1158. doi: 10.1038/s41589-018-0152-y. Epub, 2018 Nov 12. PMID:30420692 doi:http://dx.doi.org/10.1038/s41589-018-0152-y