Mononuclear iron enzymes are primary targets of hydrogen peroxide stress

Adil Anjem, James A. Imlay

Research output: Contribution to journalArticlepeer-review


This study tested whether nonredox metalloenzymes are commonly charged with iron in vivo and are primary targets of oxidative stress because of it. Indeed, three sample mononuclear enzymes, peptide deformylase, threonine dehydrogenase, and cytosine deaminase, were rapidly damaged by micromolar hydrogen peroxide in vitro and in live Escherichia coli. The first two enzymes use a cysteine residue to coordinate the catalytic metal atom; it was quantitatively oxidized by the radical generated by the Fenton reaction. Because oxidized cysteine can be repaired by cellular reductants, the effect was to avoid irreversible damage to other active-site residues. Nevertheless, protracted H2O 2 exposure gradually inactivated these enzymes, consistent with the overoxidation of the cysteine residue to sulfinic or sulfonic forms. During H2O2 stress, E. coli defended all three proteins by inducing MntH, a manganese importer, and Dps, an iron-sequestration protein. These proteins appeared to collaborate in replacing the iron atom with nonoxidizable manganese. The implication is that mononuclear metalloproteins are common targets of H2O2 and that both structural and metabolic arrangements exist to protect them.

Original languageEnglish (US)
Pages (from-to)15544-15556
Number of pages13
JournalJournal of Biological Chemistry
Issue number19
StatePublished - May 4 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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