Figure 1.
Two Possible Binding Modes for O-Biaryl Carbamate Inhibitors of FAAH (A and B) The carbamate inhibitor URB597 was modeled into the FAAH active site in two different orientations. In (A), the O-biaryl group of URB597 is located in the acyl chain binding (ACB) channel of FAAH and mimics the location of the arachidonyl chain of FAAH substrates/inhibitors [21]. In (B), the O-biaryl group of URB597 is located in the cytoplasmic access (CA) channel of FAAH, positioning the phenolic oxygen near the S217-K142 residues of the catalytic triad (S241-S217-K142) responsible for leaving group protonation. Blue, basic; red, acidic; green, hydrophobic (see [21] for more details on FAAH crystal structure).