Modeling novel quinocofactors: An overview

In recent years, three novel quinonoid cofactors, topaquinone (TPQ), trypto phan tryptophyl-quinone (TTQ), and lysine tyrosylquinone (LTQ) were identif ied in copper amine oxidase, methylamine dehydrogenase, and lysyl oxidase, respectively. The novel quinocofactors all derive through posttranslational modification of amino acid residues in the backbone of the enzymes, wherea s the previously known quinonoid coenzyme, pyrroloquinoline quinone (PQQ), is noncovalently bound to several prokaryotic dehydrogenases. The identific ation of these new redox cofactors stimulated numerous studies aimed at cha racterizing their properties and their role in substrate oxidation. Many ef forts have been made to shed light on specific points, including (i) the me chanism of posttranslational modification leading to these covalently bound quinonoid coenzymes, (ii) the structural characterization of the copper-bi nding site and the relation to quinonoid cofactor (TPQ or LTQ), (iii) catal ytic mechanism, (iv) modulation of quinocofactor reactivity by the enzyme m atrix. In all these cases, recent model studies, disclosing the basic chemi cal and physicochemical properties of compounds closely resembling the nove l quinocofactors, have greatly contributed to answering specific questions, and have offered a frame of reference for interpretation of studies of TPQ , TTQ, and LTQ in enzymatic systems. This minireview is an updated, compreh ensive account of these contributions. (C) 1999 Academic Press.