Structures of Human Monoamine Oxidase B Complexes with Selective Noncovalent Inhibitors: Safinamide and Coumarin Analogs

Abstract

Structures of human monoamine oxidase B (MAO B) in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography. These compounds competitively inhibit MAO B with Ki values in the 0.1−0.5 μM range that are 30−700-fold lower than those observed with MAO A. The inhibitors bind noncovalently to MAO B, occupying both the entrance and the substrate cavities and showing a similarly oriented benzyloxy substituent.