A simple proposal that can explain the inactivity of metal-substituted superoxide dismutases

C. K. Vance, A. F. Miller

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


We propose that the apparent catalytic inactivity of Mn- and Fe-substituted superoxide dismutases (SODs) reflects E°s that are either lower (Fe-sub-(Mn)SOD) or higher (Mn-sub-(Fe)SOD) than those of native Fe- or Mn-SODs. In support, we show that the E°of Fe-sub-(Mn)SOD (Fe substituted into Mn-SOD protein) is -240 mV vs NHE, almost 0.5 V lower than our E°of 220 mV for Fe-SOD. The E°of Fe-sub-(Mn)SOD is lower than that of O2/O2.- and therefore is sufficient to explain Fe-sub-(Mn)SOD's inactivity. Indeed, Fe-sub-(Mn)SOD is shown to be unable to oxidize O2.-. Alternate causes of inactivity are ruled out by our demonstration that Fe-sub-(Mn)SOD retains the ability to reduce O2.- Thus, the active site remains active with respect to substrate binding and proton and electron transfer. Finally, we show that Fe-sub-(Mn)SOD's inactivity with respect to O2.- oxidation cannot be solely due to competitive inhibition by OH-. Thus, our proposal provides a simple chemical basis for the observed catalytic inactivity of metal-exchanged Mn- or Fe-SODs and suggests that these strongly homologous enzymes may provide important insights into mechanisms of redox midpoint potential tuning in proteins.

Original languageEnglish
Pages (from-to)461-467
Number of pages7
JournalJournal of the American Chemical Society
Issue number3
StatePublished - Jan 28 1998

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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