Voprosy meditsinskoi khimii (ISSN 0042-8809)

Monoamine oxidase B active site modelling by means of computer moulding


1. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences
PubMed Id: 11925756
Year: 2001 vol: 47  issue:6  pages: 642-651
Abstract: Using previously developed approach for active site modelling of enzymes with unknownspatial structure (Veselovsky et al., Biochemistry (Moscow), 65, 1072-1079)substrate/inhibitor binding site of monoamine oxidase B was designed by means of computermoulding. This mould corresponds to the shape and volume size of selective substrates andinhibitors of this enzyme. Active site moulds of monoamine oxidases A and B exhibitsignificant differences in these parameters. The correctness of the resultant model ofmonoamine oxiadse B active site was validated by using three compounds which were notemployed in the training sets. Weak inhibitors were not accommodated in the mould whereastheir "flexible" analogues exhibitng rather potent inhibition are readilyaccommodated in this mould. This suggests that our mould reflects some important spatialfeatures of monoamine oxidase B active site. This mould can be employed for screening ofnew perspective inhibitior of monoamine oxidase B and pilot evaluation of their monoamineoxidase B inhibitory activity.
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Reference: Tikhonova O.V., Ivanov A.S., Medvedev A.E., Veselovsky A.V., Monoamine oxidase B active site modelling by means of computer moulding, Voprosy meditsinskoi khimii, 2001, vol: 47(6), 642-651.