Reassessment of the active site quino-cofactor proposed to occur in the Aspergillus niger amine oxidase AO-I from the properties of model compounds.
Quino-cofactors have been found in a wide variety of prokaryotic and eukaryotic organisms. Two variants have, thus far, been demonstrated to derive from tyrosine precursors: these are the 2,4, 5-trihydroxyphenylalanine quinone (topa quinone or TPQ) [Janes, S. M. , et al. (1990) Science 248, 98] and an o-quinone analogue containing the side chain of a lysine residue (lysyltyrosine quinone or LTQ) [Wang, S. Z., et al. (1996) Science 273, 1078]. Additionally, a third variant of the family of tyrosine-derived cofactors has been reported to exist in an Aspergillus niger amine oxidase AO-I. This was described as an o-quinone cross-linked to the side chain of a glutamate residue [Frebort, I. (1996) Biochim. Biophys. Acta 1295, 59]. We have synthesized model compounds related to the proposed structure. Characterization of the redox properties for the model compound and spectral properties of its 4-nitrophenylhydrazine derivative lead us to conclude that the cofactor in A. niger amine oxidase AO-I has been misidentified. A TPQ carboxylate ester is considered an unlikely candidate for a biologically functional quino-cofactor.
Melville
C R
CR
Department of Chemistry, University of California, Berkeley 94720, USA.
Green
E L
EL
Sanders-Loehr
J
J
Klinman
J P
JP
D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry / Q000378:metabolism*; D001234:Aspergillus niger / Q000201:enzymology*; D001665:Binding Sites; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation
C086758:2,4,5-trihydroxyphenylalanine quinone; D004295:Dihydroxyphenylalanine; D006631:Amine Oxidase (Copper-Containing)