Reaction of AdoMet with ThiC generates a backbone free radical

Biochemistry. 2009 Jan 20;48(2):217-9. doi: 10.1021/bi802154j.


ThiC is an [4Fe-4S] cluster protein that catalyzes the formation of 4-amino-5-hydroxymethyl-2-methylpyrimidine. EPR spectroscopic studies demonstrate that, upon interaction with AdoMet, active ThiC from Salmonella enterica generates a persistent free radical on the alpha-carbon of an amino acid residue. The EPR properties of the radical are consistent with any residue other than a Gly or Ala. Exposure to oxygen was accompanied by a fission of the radical-carrying polypeptide chain between the Gly436 and His437 residues in ThiC. Regardless of whether the backbone radical is part of the catalytic machinery, its presence provides evidence that ThiC employs free radical chemistry as expected for radical SAM enzymes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Electron Spin Resonance Spectroscopy
  • Free Radicals / metabolism*
  • Intramolecular Transferases / metabolism
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / metabolism*
  • Models, Molecular
  • Oxidation-Reduction
  • Oxygen / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • S-Adenosylmethionine / chemistry
  • S-Adenosylmethionine / metabolism*
  • Salmonella enterica / metabolism
  • Thermodynamics


  • Free Radicals
  • Iron-Sulfur Proteins
  • S-Adenosylmethionine
  • Intramolecular Transferases
  • Oxygen