A new redox cofactor in eukaryotic enzymes: 6-hydroxydopa at the active site of bovine serum amine oxidase.
An active site, cofactor-containing peptide has been obtained in high yield from bovine serum amine oxidase. Sequencing of this pentapeptide indicates: Leu-Asn-X-Asp-Tyr. Analysis of the peptide by mass spectrometry, ultraviolet-visible spectroscopy, and proton nuclear magnetic resonance leads to the identification of X as 6-hydroxydopa. This result indicates that, contrary to previous proposals, pyrroloquinoline quinone is not the active site cofactor in mammalian copper amine oxidases. Although 6-hydroxydopa has been implicated in neurotoxicity, the data presented suggest that this compound has a functional role at an enzyme active site.
Janes
S M
SM
Department of Chemistry, University of California, Berkeley 94720.
Mu
D
D
Wemmer
D
D
Smith
A J
AJ
Kaur
S
S
Maltby
D
D
Burlingame
A L
AL
Klinman
J P
JP
D006631:Amine Oxidase (Copper-Containing); D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003300:Copper; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis / Q000138:chemical synthesis; D011809:Quinones / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
D010446:Peptide Fragments; D011809:Quinones; C001388:6-hydroxydopa; D004295:Dihydroxyphenylalanine; D003300:Copper; D010088:Oxidoreductases; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors