Catalytic turnover of benzylamine by a model for the lysine tyrosylquinone(LTQ) cofactor of lysyl oxidase

Lysyl oxidase differs from other copper an-tine oxidases in that its active quinone cofactor reflects cross-linking of a lysyl residue into the tyrosi ne-derived quinone nucleus found in the plasma and other copper amine oxida ses. A model for the lysyl oxidase cofactor (LTQ), 3,3-dimethyl-2,3-dihydro indole-5,6-quinone (4), was synthesized and found to be stable to both hydr olysis and oxidation events that prevent simpler models from functioning as turnover catalysts. We show that 4 catalyzes the aerobic oxidative deamina tion of benzylamine, though turnover eventually ceases on account of oxidat ion of the dihydrobenzoxazole tautomer of the "product Schiff base" to form a benzoxazole, a reaction that may be physiologically relevant. The mechan ism of the overall reaction profile was elucidated by a combination of opti cal and NMR spectroscopy and O-2 uptake studies.