The discovery of 2, 4, 5-trihydoxyphenylalanine quinone, or topaquinone [TPQ (1)] 1 in copper amine oxidases (CAOs) defined a new class of enzymatic redox cofactors derived from the post-translational modification of tyrosine or tryptophan protein side chains to form quinonoid structures. Figure 1A shows the structures of the cofactors which have been characterized, namely, TPQ, lysine tyrosyl quinone [LTQ, formed via the cross-linking of a tyrosine and a lysine side chain (2)], tryptophan tryptophyl quinone [TTQ, formed via the cross-linking of two tryptophan side chains (3)], and cysteine tryptophyl quinone [CTQ, formed via the crosslinking of a cysteine and a tryptophan side chain (4)]. It has been shown that TPQ formation in CAOs proceeds through a copper-ion-dependent autoxidation which does not require another enzyme (5, 6). The details of the mechanism of TPQ biogenesis are less well established than …