Wessel A C Burger, Vi Pham, Ziva Vuckovic, Alexander S Powers, Jesse I Mobbs, Yianni Laloudakis, Alisa Glukhova, Denise Wootten, Andrew B Tobin, Patrick M Sexton, Steven M Paul, Christian C Felder, Radostin Danev, Ron O Dror, Arthur Christopoulos, Celine Valant, David M Thal
The M4 muscarinic acetylcholine receptor (M4 mAChR) has emerged as a drug target of high therapeutic interest due to its expression in regions of the brain involved in the regulation of psychosis, cognition, and addiction. The mAChR agonist, xanomeline, has provided significant improvement in the Positive and Negative Symptom Scale (PANSS) scores in a Phase II clinical trial for the treatment of patients suffering from schizophrenia. Here we report the active state cryo-EM structure of xanomeline bound to the human M4 mAChR in complex with the heterotrimeric Gi1 transducer protein...
September 6, 2023: Nature Communications