[摘要]：Mechanistic and structural studies have been carried out to investigate the mol. basis for the irreversible inhibition of human MAO-B by mofegiline. Competitive inhibition with substrate shows an apparent Ki of 28 nM. Irreversible inhibition of MAO-B occurs with a 1:1 M stoichiometry with no observable catalytic turnover. The absorption spectral properties of mofegiline inhibited MAO-B show features (lmax x 450 nm) unlike those of traditional flavin N(5) or C(4a) adducts. Visible and near-UV CD spectra of the mofegiline-MAO-B adduct shows a neg. peak at 340 nm with an intensity similar to that of N(5) flavocyanine adducts. The x-ray crystal structure of the mofegiline-MAO-B adduct shows a covalent bond between the flavin cofactor N(5) with the distal allylamine carbon atom as well as the absence of the fluorine atom. A mechanism to explain these structural and spectral data is proposed.
