The source of the oxygen atom in the α-hydroxyglycine intermediate of the peptidylglycine α-amidating reaction

M. Noguchi, H. Seino, H. Kochi, H. Okamoto, T. Tanaka, M. Hirama

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Peptidylglycine α-amidating activity catalyses the oxidation of a C-terminally glycine-extended peptide to a desglycine α-amidated peptide at the expense of ascorbate and O2 in the presence of Cu2+. The reaction involves oxidative N-dealkylation within the terminal glycine residue with retention of the glycine N atom and release of the remainder as glyoxylate. Recent studies by us and others have revealed that the reaction consists of two steps via a carbinolamide as an intermediate (peptidyl α-hydroxyglycine), and also that two separate enzymes derived from a common precursor protein catalyse these steps, formation of the carbinolamide and its conversion into α-amide and glyoxylate. As for the mechanism of carbinolamide formation, two distinct pathways can be considered: direct mono-oxygenation at the glycine α-C atom and dehydrogenation leading to an imine followed by hydration. To draw a distinction between them, we carried out the reaction with D-Tyr-Val-Gly as the substrate either in the H218O-enriched medium or under an atmosphere of 18O2, and isolated the α-hydroxyglycine intermediate. The fast-atom-bombardment mass-spectral analyis demonstrated that the hydroxy O atom comes from O2, but not from H2O, indicating that the α-hydroxylation should be a mono-oxygenase reaction.

Original languageEnglish
Pages (from-to)883-888
Number of pages6
JournalBiochemical Journal
Volume283
Issue number3
DOIs
Publication statusPublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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