Structure, function, and applications of tryptophan tryptophylquinone enzymes

Tryptophan and tyrosine residues in proteins may be posttranslationally modified to form enzyme cofactors. Tryptophan tryptophylquinone (TTQ), the cofactor of methylamine dehydrogenase (MADH), is formed by covalent cross-linking of two tryptophan residues and incorporation of two oxygen atoms into one of the indole rings to form a quinone. MADH converts primary amines to their corresponding aldehydes plus ammonia. During the catalytic cycle, TTQ mediates electron transfer from substrate to a copper protein, amicyanin. These electrons are transferred to the respiratory chain via a c-type cytochrome. Structural, kinetic and site-directed mutagenesis studies have characterized protein-protein interactions, and mechanisms of catalysis and electron transfer by TTQ. Preliminary results obtained with MADH enzyme-electrodes demonstrate the potential for quinoprotein-based biosensors.