FrsA functions as a cofactor-independent decarboxylase to control metabolic flux

Nat Chem Biol. 2011 May 29;7(7):434-6. doi: 10.1038/nchembio.589.

Abstract

The interaction between fermentation-respiration switch (FrsA) protein and glucose-specific enzyme IIA(Glc) increases glucose fermentation under oxygen-limited conditions. We show that FrsA converts pyruvate to acetaldehyde and carbon dioxide in a cofactor-independent manner and that its pyruvate decarboxylation activity is enhanced by the dephosphorylated form of IIA(Glc) (d-IIA(Glc)). Crystal structures of FrsA and its complex with d-IIA(Glc) revealed residues required for catalysis as well as the structural basis for the activation by d-IIA(Glc).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaldehyde / metabolism
  • Animals
  • Base Sequence
  • Carbon Dioxide / metabolism
  • Carboxy-Lyases / chemistry
  • Carboxy-Lyases / genetics
  • Carboxy-Lyases / metabolism*
  • Carboxy-Lyases / pharmacology
  • Crystallography, X-Ray
  • Decarboxylation
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Female
  • Fermentation
  • Glucose / metabolism*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred ICR
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoenolpyruvate Sugar Phosphotransferase System / chemistry
  • Phosphoenolpyruvate Sugar Phosphotransferase System / genetics
  • Phosphoenolpyruvate Sugar Phosphotransferase System / metabolism*
  • Protein Conformation
  • Pyruvic Acid / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Recombinant Proteins / pharmacology
  • Substrate Specificity
  • Vibrio vulnificus / genetics
  • Vibrio vulnificus / metabolism
  • Vibrio vulnificus / pathogenicity
  • Virulence

Substances

  • Escherichia coli Proteins
  • Recombinant Proteins
  • crr protein, E coli
  • Carbon Dioxide
  • Pyruvic Acid
  • Phosphoenolpyruvate Sugar Phosphotransferase System
  • Carboxy-Lyases
  • Acetaldehyde
  • Glucose

Associated data

  • GENBANK/HM172799
  • PDB/3MVE
  • PDB/3OUR