It has been reported that cation radicals of aromatic substrates maintain the active form of lignin peroxidase by oxidatively converting compound III, generated during peroxidase turnover, into ferric enzyme (D. P. Barr and S. D. Aust, 1994, Arch. Biochem. Biophys. 312, 511-515). In this work, we investigated protective mechanisms for manganese peroxidase. Oxidation of Mn(II) by manganese peroxidase displayed complex kinetics, which were explained by accumulation of compound III followed by its reactivation by the enzymatically produced Mn(III). Conversion of compound III to ferric enzyme by Mn(III) was not observed for lignin peroxidase or heme propionate-modified recombinant manganese peroxidase, suggesting that Mn(III) may interact with compound III of native manganese peroxidase at a heme propionate to oxidize iron-coordinated superoxide via long-range electron transfer. Additionally, Mn(II) also reactivated compound III. Although this reaction was slower, it could prevent compound III accumulation when excess Mn(II) was present. Another protective mechanism for manganese peroxidase is proposed for insufficient chelator conditions. In contrast to effective Mn(II) chelators, low-affinity ligands supported considerably slower enzyme turnover, and Mn(III) released was more reactive with hydrogen peroxide, resulting in a catalase-type reaction. Reactivation of compound III and catalatic activity may provide biologically relevant mechanisms for protection of manganese peroxidase against suicidal inactivation by hydrogen peroxide under a variety of manganese and oxalate conditions.