Crystal structure of the M₅ muscarinic acetylcholine receptor.

ABSTRACT: The human M₅ muscarinic acetylcholine receptor (mAChR) has recently emerged as an exciting therapeutic target for treating a range of disorders, including drug addiction. However, a lack of structural information for this receptor subtype has limited further drug development and validation. Here we report a high-resolution crystal structure of the human M₅ mAChR bound to the clinically used inverse agonist, tiotropium. This structure allowed for a comparison across all 5 mAChR family members that revealed important differences in both orthosteric and allosteric sites that could inform the rational design of selective ligands. These structural studies, together with chimeric swaps between the extracellular regions of the M₂ and M₅ mAChRs, provided

SUBMITTER: Vuckovic Z 

PROVIDER: S-EPMC6926013 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature