Send to

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2004 Mar 25;47(7):1767-74.

Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.

Author information

Department of Genetics and Microbiology, University of Pavia, Via Abbiategrasso 207, Pavia, 27100 Italy.


Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons


    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Support Center