On the Mechanism of Action of Superoxide Dismutase: A Theoretical Study

Roman Osman, Harold Basch

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80 Scopus citations


Quantum chemical studies of the interaction of superoxide radical anion with a model of the active site of superoxide dismutase (SOD) suggest a new mechanism of action of the enzyme. The model for the active site of SOD was constructed from the crystal structure of the enzyme, and it contains the copper with its ligands, a model for the zinc ion, and an ammonium group as a model for Arg-141. The simulation of the enzymatic mechanism indicates that the presence of Arg-141 is responsible for a change in the redox chemistry of superoxide. In the absence of Arg-141, superoxide can reduce the copper and dissociate as oxygen. In its presence, however, the superoxide does not reduce the copper and forms a stable complex with the enzyme. This stable intermediate oxidizes another superoxide to oxygen with a concomitant reduction of the cupric to cuprous ion. In the resulting reduced form of the complex, superoxide has an increased proton affinity that induces proton transfer from Arg-141 to the superoxide. This form undergoes a charge redistribution that forms a complex between the oxidized form of the enzyme and a hydroperoxide anion. The enzymatic cycle is completed by the dissociation of hydrogen peroxide and the regeneration of the native enzyme. The stable complex between the enzyme and superoxide plays an important role in the activation of superoxide and can explain metal-mediated superoxide toxicity.

Original languageEnglish
Pages (from-to)5710-5714
Number of pages5
JournalJournal of the American Chemical Society
Issue number19
StatePublished - 1 Sep 1984


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