Abstract
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 language | English |
---|---|
Pages (from-to) | 461-467 |
Number of pages | 7 |
Journal | Journal of the American Chemical Society |
Volume | 120 |
Issue number | 3 |
DOIs | |
State | Published - Jan 28 1998 |
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry