[Modeling of monoamine oxidase B active site by computer moulding]

Using previously developed approach for active site modelling of enzymes with unknown spatial structure (Veselovsky et al., Biochemistry (Moscow), 65, 1072-1079) substrate/inhibitor binding site of monoamine oxidase B was designed by means of computer moulding. This mould corresponds to the shape and volume size of selective substrates and inhibitors of this enzyme. Active site moulds of monoamine oxidases A and B exhibit significant differences in these parameters. The correctness of the resultant model of monoamine oxiadse B active site was validated by using three compounds which were not employed in the training sets. Weak inhibitors were not accommodated in the mould whereas their "flexible" analogues exhibitng rather potent inhibition are readily accommodated in this mould. This suggests that our mould reflects some important spatial features of monoamine oxidase B active site. This mould can be employed for screening of new perspective inhibitior of monoamine oxidase B and pilot evaluation of their monoamine oxidase B inhibitory activity.