Fig. 1
From: Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
Allosteric pockets in mAChR crystal structures are similar in shape. a An allosteric binding site of the M1 mAChR is located on the extracellular side of the receptor, in the extracellular vestibule (ECV). This ECV allosteric site, located between ECL2, TM2, TM6, and TM7, is adjacent to but distinct from the orthosteric binding site. b The ECV allosteric pockets observed in the crystal structures of the inactive M1, M2, M3, and M4 mAChRs are similar in shape (pocket surface displayed in gray with selected side chains shown as sticks). c LY2119620, a PAM crystallized in complex with the agonist-bound active-state M2 mAChR, is planar in shape, similar to many other known mAChR PAMs. d In contrast to LY2119620, BQZ12 and similar M1-selective PAMs are distinctly nonplanar
