Figure 5.

Comparison of the Ligand-Binding Modes of CB₁ and CB₂

(A and B) (A) Superposition of AM6538@CB₁ (5TGZ) (blue) and AM10257@CB₂ (5ZTY) (orange) ligand-binding pockets and (B) conformational difference of F200 and W258 in antagonist bound CB₂ and CB₁.

(C) Comparison of the “toggle switch” residue conformation in agonist AM12033@CB₂ (6KPC) (gold) and AM10257@CB₂ (5ZTY) (orange). (D–G) (D) WIN55212-2@CB₂ (6PT0) (yellow) orthosteric pocket shows the direct contact of the ligand with residues F117^3.36 and W258^6.48 compared with AM10257@CB₂ (orange). Comparison of the gross morphology of the receptors: (E) active CB₁ and CB₂ (F), active CB₁ and inactive CB₂, and (G) inactive CB₁ and CB₂. Data used to prepare the figures were obtained from Li et al. (2019), Figures 5A and 5B; Hua et al. (2020), Figures 5C and 5E–5G; and Xing et al. (2020), Figure 5D.