Tyrosine-Derived Quinone Cofactors

Copper amine oxidases (CAOs) and lysyl oxidase (LOX) both contain Cu2+ and quinone cofactors that are derived from a tyrosine residue in the active site. In CAOs, the cofactor is 2,4,5-trihydroxyphenylalanine quinone (TPQ), and in LOX it is lysine tyrosyl quinone (LTQ). The mechanism of oxidative deamination by CAOs is well understood, but there is a controversy surrounding the role of Cu2+ in cofactor reoxidation. The chemistry of LTQ in LOX, by contrast, has not been as extensively studied. This Account discusses the strategies that CAOs have evolved to control the mobility of TPQ to optimize activity. In addition, some recent studies on CAOs whose active-site Cu2+ has been replaced with Co2+ or Ni2+ are summarized. Finally, there is a discussion on the properties of a model compound of LTQ and their relevance to the chemistry of LOX.