A New Redox Cofactor in Eukaryotic Enzymes: 6-Hydroxydopa at the Active Site of Bovine Serum Amine Oxidase

Janes, Susan; Mu, David; Wemmer, David E.; Smith, Alan Jay; Kaur, Surinder; Maltby, David; Burlingame, Alma L.; Klinman, Judith P.

doi:10.1126/science.2111581

Cited by 666 publications

(423 citation statements)

References 34 publications

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“…PQQ was not found when the structure of the zucchini AOase was solved (Messerschmidt et al, 1989). Janes et al (1990) recently showed that bovine serum amine oxidiase, which has been suggested to be a quinoprotein, has 6-hydroxydopa instead of PQQ as its cofactor. They suggested that this could also be true for other mammalian copper oxidases that have been characterized as quinoproteins.…”

Section: Possible Binding Site Of' the Prosthetic Group Pqqmentioning

confidence: 99%

Isolation and structural analysis of the laccase gene from the ligninegrading fungus Phlebia radiata

Saloheimo

Niku‐Paavola

Knowles

1991

Journal of General Microbiology

127

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We have isolated and characterized a gene coding for the laccase of the lignin-degrading fungus Phlebia radiaftr, The gene has nine introns and recognizable fungal promoter elements. Sequences homologous to the consensus eukaryotic heat-shock regulatory element can be found in the promoter. RNA hybridization results indicate that this gene is regulated at the transcriptional level. The derived laccase amino acid sequence shows homology to plant ascorbate oxidases, suggesting that the basic structure of the laccase is similar to the three-fold repeated P-barrel of the ascorbate oxidases. Potential copper ligands and a residue carrying the prosthetic group pyrroloquinoline quinone (PQQ) in the laccase protein can be identified by homology. The intron/exon structure of the laccase gene suggests that this protein could have evolved by exon shuffiing.

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Section: Possible Binding Site Of' the Prosthetic Group Pqqmentioning

confidence: 99%

Isolation and structural analysis of the laccase gene from the ligninegrading fungus Phlebia radiata

Saloheimo

Niku‐Paavola

Knowles

1991

Journal of General Microbiology

127

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“…Copper amine oxidases (AOs) are a widely distributed class the precursor of topaquinone was then confirmed by comparative studies of DNA and protein sequences from lentil seedling, of quinoproteins that convert primary amines to the corresponding aldehydes, ammonia and hydrogen peroxide (McIntire and bovine serum, human and porcine kidney (Rossi et al, 1992;Mu et al, 1994). Hartmann, 1993;Klinman and Mu, 1994).…”

mentioning

confidence: 98%

“…Hartmann, 1993;Klinman and Mu, 1994). After the identification of the active-site cofactor of bovine plasma amine oxidase Following these findings, by using inactive precursor forms of bacterial amine oxidases, Tanizawa and co-workers demonas the quinone of 2,4,5-trihydroxyphenylalanine (topaquinone) (Janes et al, 1990), topaquinone was reported to be present in strated the generation of topaquinone through the self-processing of the protein with the participation of the copper ion in the all AOs so far investigated (Janes et al, 1992;Knowles and Dooley, 1994). Also lysyl oxidase, a physiologically important active-site (Matsuzaki et al, 1994(Matsuzaki et al, , 1995.…”

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confidence: 99%

Biosynthesis of the topaquinone cofactor in copper amine oxidases

Rinaldi

Porcu

Oliva

et al. 1998

European Journal of Biochemistry

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Copper amine oxidases utilize 2,4,5-trihydroxyphenylalanine quinone (topaquinone) as a cofactor in enzymatic catalysis. This cofactor is formed from a tyrosine residue through a self-catalytic mechanism with the participation of the copper ion at the active site. Although pathways have been postulated for topaquinone biogenesis, portions of this scheme are still unclear. We utilized 4-tert-butyl-derived models for the putative intermediates of topaquinone generation and studied the effect of Cu(II) and Zn(II) ions on each autoxidative step from dopa-to topaquinone-like compounds at physiological pH (7.4). Several polyvinyl-alcohol-based soluble resins bearing mono-and di-hydroxyphenolic moieties were also prepared, and their tendency to give hydroxyquinonic structures when incubated at alkaline pH values was investigated. Our results confirm (although indirectly) the formation of dopa and dopaquinone during topaquinone biosynthesis. Moreover, we collected evidence that, following the formation of dopa, the role of the active-site copper ion in topaquinone biogenesis would be limited to the catalysis of the two subsequent quinonization steps (i.e. from dopa to dopaquinone and from topa to topaquinone), thus disfavoring the possibility of a direct intervention of the metal ion in the hydroxylation of dopaquinone. In particular, Cu(II) was shown to influence deeply the autoxidation of 1,2,5-trihydroxy-4-tert-butylbenzene, used as model of topa, both increasing the reaction rate and changing its mechanism. The mechanistic implications of these findings for the biogenesis of topaquinone and its analogs at the active site of various amine oxidases are discussed.

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“…Copper ion and an organic cofactor topaquinone [2], which is formed by autooxidation of a specific tyrosyl residue [3], mediate the catalytic reaction proceeding by a pingpong mechanism with Cu(I)-semiquinone as an intermediate [4]. A complete amino acid sequence has become available for several amine oxidases [5] and recently the crystal structure of the amine oxidase from Escherichia coli has been determined in both active and inactive forms [6].…”

Section: Introductionmentioning

confidence: 99%

The fungus Gibberella fujikuroi produces copper/topaquinone‐containing amine oxidase when induced by n‐butylamine

1997

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SUMMARYCrude extract of Gibberellafujikuroi AKU 3802 mycelium induced with n-butylamine showed a single amine oxidase activity band in a non-denaturing gel that cross-reacted with the antibody against copper/topaquinone-containing amine oxidase from AspergiUus niger. The enzyme was purified by a procedure involving four chromatographic steps. Purified enzyme was pink with an absorption maximum at 490 nm. Molecular mass of 135 kDa estimated by gel chromatography and 70 kDa found by SDS-PAGE confirmed the dimeric structure of the enzyme. The enzyme readily oxidized n-hexylamine, n-butylamine, benzylamine and histamine, but not spermine or spermidine. Inactivation by carbonyl reagents and copper chelators suggested the presence of a copper/topaquinone cofactor. Spectrophotometric titration by p-nitrophenylhydrazine showed one reactive carbonyl group per subunit and redox-cyclic quinone staining confirmed the presence of a quinone cofactor, pH-dependent shift of the absorption spectrum of the enzyme pnitrophenylhydrazone (465 nm at neutral to 580 nm at alkaline pH) supports the identity of the cofactor with topaquinone. The N-terminal amino acid sequence of the enzyme showed high similarity to other microbial copper/topaquinone-containing amine oxidases.

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A New Redox Cofactor in Eukaryotic Enzymes: 6-Hydroxydopa at the Active Site of Bovine Serum Amine Oxidase

Cited by 666 publications

References 34 publications

Isolation and structural analysis of the laccase gene from the ligninegrading fungus Phlebia radiata

Isolation and structural analysis of the laccase gene from the ligninegrading fungus Phlebia radiata

Biosynthesis of the topaquinone cofactor in copper amine oxidases

The fungus Gibberella fujikuroi produces copper/topaquinone‐containing amine oxidase when induced by n‐butylamine

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