Structure and biogenesis of topaquinone and related cofactors

The structure of a new biological redox cofactor - topaquinone (TPQ), the q uinone of 2,4,5-trihydroxyphenylalanine - was elucidated in 1990. TPQ is th e cofactor in most copper-containing amine oxidases. It is produced by post -translational modification of a strictly conserved active-site tyrosine re sidue. Recent work has established that TPQ biogenesis proceeds via a novel self-processing pathway requiring only the protein, copper, and molecular oxygen. The oxidation of tyrosine to TPQ by dioxygen is a six-electron proc ess, which has intriguing mechanistic implications because copper is a one- electron redox agent, and dioxygen can function as either a two-electron or four-electron oxidant. This review adopts an historical perspective in dis cussing the structure and reactivity of TPQ in amine oxidases, and then ass esses what is currently understood about the mechanism of the oxidation of tyrosine to produce TPQ. Aspects of the structures and chemistry of related cofactors, such as the Tyr-Cys radical in galactose oxidase and the lysine tyrosylquinone of lysyl oxidase, are also discussed.