Quinone Cofactors


Quinone cofactors are used by several classes of enzymes, which catalyse the oxidation of biogenic amines and alcohols, to help catalyse these reactions. Before 1990 only one cofactor, the peptide‐derived pyrroloquinoline quinone had been identified. During 1990–2001, however, four new quinone prosthetic groups derived from naturally occurring amino acids were discovered. The first protein‐derived, nondissociable cofactor identified was 2,4,5‐trihydroxyphenylalanine quinone, designated topaquinone (TPQ) in copper amine oxidases. The discovery of TPQ led to the identification of a series of new quinone cofactors, including lysine tyrosylquinone (LTQ) in lysyl oxidase, cysteine tryptophylquinone (CTQ) in quinohaemoprotein amine dehydrogenase and tryptophan tryptophylquinone (TTQ) in bacterial methylamine dehydrogenase. These cofactors contribute electrophillic capabilities (and stabilise free radical intermediates) that naturally occurring, unmodified amino acid side chains are unable to provide.

Key Concepts:

  • Quinone cofactors are a class of cofactors used by many enzymes to catalyse the oxidation of amines and alcohols.

  • Five quinone cofactors have been characterised: PQQ, TPQ, LTQ, TTQ and CTQ.

  • PQQ is a peptide‐derived cofactor that involves the expression of six genes located within an operon.

  • TPQ is derived from a precursor tyrosine and requires only Cu2+ and O2 for biogenesis.

  • LTQ is formed by the cross‐linking of a tyrosine residue and a lysine residue, also requiring only Cu2+ and O2.

  • TTQ is formed by the cross‐linking of two tryprophan resides, with MauG completing biogenesis.

  • CTQ, the most recently discovered quinone cofactor, is formed by the cross‐linking of a cysteine reside and a tryptophan residue.

Keywords: structure and function; catalytic mechanisms; biogenesis; model compounds

Figure 1.

Structures of quinocofactors. The structures of topaquinone (TPQ), lysine tyrosylquinone (LTQ), tryptophan tryptophylquinone (TTQ), cysteine tryptophylquinone (CTQ) and pyrroloquinoline quinone (PQQ) are shown.

Figure 2.

Working mechanism for the generation of TPQ from its tyrosine precursor in HPAO (Dove et al., ; Schwartz et al., ).

Figure 3.

Simulated annealing omit map for a new active site structure observed during biogenesis of HPAO Y305F expressed in E. coli. Reprinted with permission from Chen et al., . © 2010 American Chemical Society.

Figure 4.

(a) Postulated mechanism for the branching of a biogenesis intermediate to TPQ and TPO. (b) Model to explain 3,4‐dihydroperoxo‐prouct. (c) Model to explain 2,4‐dihydroperoxo‐product. Reprinted with permission from Chen et al., . © 2010 American Chemical Society.

Figure 5.

Proposed catalytic mechanism of the CAO from H. polymorpha (Mure et al., ). In CAOs from other sources, it is proposed that the reduced aminophenol first reduces Cu2+ to Cu1+, which then reacts with O2 to yield the Cu2+ (Dooley et al., ).



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Further Reading

Anthony C (1996) Quinoprotein‐catalysed reactions. Biochemical Journal 320(Pt3): 697–711.

Davidson VL (2007) Protein‐derived cofactors. Expanding the scope of post‐translational modifications. Biochemistry 46(18): 5283–5292.

Davidson VL (ed.) (1993) Principles and Applications of Quinoproteins. New York: Marcel Dekker.

Klinman JP (1996) New quinocofactors in eukaryotes. Journal of Biological Chemistry 271(44): 27189–27192.

Klinman JP (2003) The multi‐functional topa‐quinone copper amine oxidases. Biochimica et Biophysica Acta 1647(1‐2): 131–137.

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Lang, Albert, and Klinman, Judith P(Feb 2013) Quinone Cofactors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000660.pub2]