title: Computer modelling and visualization of active site of monoamine oxidases.
abstract: In spite of significant progress in MAO research culminating in the crystallization of the MAO B, many structure-functional aspects of these enzymes still require better characterization. Computer modelling of the substrate/inhibitory binding region of the active site includes consensus overlay of several series of fully reversible and/or tightly bound inhibitors onto a rigid referent inhibitor(s). The shape of resultant mould obviously reflects spatial characteristic features of the substrate/inhibitor binding region. The comparison of the active site mould of MAO B with its crystal structure revealed correctness of this approach. The resultant moulds may be effectively used for virtual screening of molecular databases for new lead-structures. Using this approach we have found several selective MAO A inhibitors in databases and these compounds have never been tested for MAO inhibitory activity.
authors.affiliation: VN Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya str 10, Moscow, Russia. veselov@ibmh.msk.su
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Veselovsky
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: Alexei E
authors.initials: AE
authors.lastname: Medvedev
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008995:Monoamine Oxidase