Figure 3.

The active site of monoamine oxidase B with docked 3-phenylcoumarin derivatives. (A) A negative image of the MAO-B active site shown as a transparent surface indicates the space available for inhibitor binding with docked derivative 1 (ball-and-stick model; Figure 2). (B) A cross section, showing half of the active site, displays the contours (opaque surface) that roughly match the inhibitor shape and conformation. The colored sectors highlight specific sections of the cavity dedicated to different aspects of the 3-phenylcoumarin derivative binding: 3-phenyl ring (orange), the R4-R7 groups of the 3-phenyl ring (red), coumarin ring (yellow), the hydrophobic niche occupied by the R1/R2-groups of the coumarin ring (green). (C) A negative image of the MAO-A active site shows that only two residue changes (Ile199 → Phe208; Leu164 → Phe173) are enough to prevent 3-phenylcoumarin analog binding. (D) The docked poses of the 23 most potent 3-phenylcoumarin derivatives show what space is collectively occupied by the new inhibitors. See Figure 1 for details.