Structures of Human Monoamine Oxidase B Complexes with Selective Noncovalent Inhibitors: Safinamide and Coumarin Analogs
Claudia Binda(University of Bari Aldo Moro), Jin Wang(University of Pavia), Leonardo Pisani(Emory University), Carla Caccia(Emory University), Angelo Carotti(University of Bari Aldo Moro), Patricia Salvati(Emory University), Dale E. Edmondson(Emory University), Andrea Mattevi(University of Pavia)
Cited by 590Open Access
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.
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