Mechanism of post-translational quinone formation in copper amine oxidases and its relationship to the catalytic turnover.

Copper amine oxidases (CAOs) post-translationally construct a redox-active quinone from an amino acid side chain in their polypeptide chain. As such, these enzymes illustrate how nature is able to expand upon naturally-occurring side chains to create new, catalytically powerful functionalities. The active sites of the CAOs are highly unusual in their ability to catalyze two very different reactions: single-turnover, oxygen-dependent quinone formation, followed by catalytic oxidation (formally dehydrogenation) of amines. This review summarizes our current understanding of the pathway whereby the 2,4,5-trihydroxyphenylalanyl quinone (TPQ) cofactor is generated from the phenolic side chain of tyrosine. This reaction occurs spontaneously intermediates in the presence of O(2) and active site bound Cu(II), without the assistance of other proteins or cofactors. Ongoing work has focused on uncovering the details of the TPQ formation mechanism. A larger goal is to understand how a single active site is capable of supporting both quinone formation and subsequent catalytic turnover.