Candidate nAChR agonist, specific for beta2-containing subtypes. A: Chemical structure of 1. B: Details of the interactions between 1 (gray) and alpha4-beta2 nAChR agonist binding pocket (gold: alpha4, cyan: beta2). 1 occupies the same pocket as docked nicotine (magenta), and presents a pyridine extension (circled in black) that fits next to Ala 135 of beta-2, but clashes with Leu 135 of beta-4 (white), or Val 135 of alpha-7 (not shown). An amide group of 1 fills the pocket occupied by a water molecule when nicotine or acetylcholine are bound (Figure 3 – Left) and makes a network of hydrogen-bonds (black lines) with the receptor.C: Same view and orientation as in B, with a skin representation of the binding pocket.D: Same as C, with alpha4-beta4 nAChR binding pocket: the steric clash between the receptor and the pyridine moiety of the ligand is visible.
Schapira et al. BMC Structural Biology 2002 2:1 doi:10.1186/1472-6807-2-1