A concerted mechanism for berberine bridge enzyme

Nat Chem Biol. 2008 Dec;4(12):739-41. doi: 10.1038/nchembio.123. Epub 2008 Oct 26.

Abstract

Berberine bridge enzyme catalyzes the conversion of (S)-reticuline to (S)-scoulerine by formation of a carbon-carbon bond between the N-methyl group and the phenolic ring. We elucidated the structure of berberine bridge enzyme from Eschscholzia californica and determined the kinetic rates for three active site protein variants. Here we propose a catalytic mechanism combining base-catalyzed proton abstraction with concerted carbon-carbon coupling accompanied by hydride transfer from the N-methyl group to the N5 atom of the FAD cofactor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Berberine Alkaloids
  • Catalysis
  • Catalytic Domain
  • Eschscholzia / enzymology*
  • Flavin-Adenine Dinucleotide / metabolism
  • Kinetics
  • Oxidoreductases, N-Demethylating / chemistry
  • Oxidoreductases, N-Demethylating / metabolism
  • Oxygen
  • Protons

Substances

  • Alkaloids
  • Berberine Alkaloids
  • Protons
  • Flavin-Adenine Dinucleotide
  • discretamine
  • reticuline oxidase
  • Oxidoreductases, N-Demethylating
  • Oxygen

Associated data

  • PubChem-Substance/56242089
  • PubChem-Substance/56242090
  • PubChem-Substance/56242091
  • PubChem-Substance/56242092
  • PubChem-Substance/56242093
  • PubChem-Substance/56242094
  • PubChem-Substance/56242095
  • PubChem-Substance/56242096
  • PubChem-Substance/56242097
  • PubChem-Substance/56242098
  • PubChem-Substance/56242099
  • PubChem-Substance/56242100
  • PubChem-Substance/56242101