Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs.
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 microM 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.
Binda
Claudia
C
Department of Genetics and Microbiology, University of Pavia, via Ferrata 1, Pavia, 27100 Italy.
Wang
Jin
J
Pisani
Leonardo
L
Caccia
Carla
C
Carotti
Angelo
A
Salvati
Patricia
P
Edmondson
Dale E
DE
Mattevi
Andrea
A
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D001596:Benzylamines / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry*; D011485:Protein Binding
D001596:Benzylamines; D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; C092797:safinamide; D008995:Monoamine Oxidase; D000409:Alanine