Ferritins are iron storage proteins that overcome the problems of toxicity and poor bioavailability of iron by catalyzing iron oxidation and mineralization through the activity of a diiron ferroxidase site. Unlike in other ferritins, the oxidized di-Fe(3+) site of Escherichia coli bacterioferritin (EcBFR) is stable and therefore does not function as a conduit for the transfer of Fe(3+) into the storage cavity, but instead acts as a true catalytic cofactor that cycles its oxidation state while driving Fe(2+) oxidation in the cavity. Herein, we demonstrate that EcBFR mineralization depends on three aromatic residues near the diiron site, Tyr25, Tyr58, and Trp133, and that a transient radical is formed on Tyr25. The data indicate that the aromatic residues, together with a previously identified inner surface iron site, promote mineralization by ensuring the simultaneous delivery of two electrons, derived from Fe(2+) oxidation in the BFR cavity, to the di-ferric catalytic site for safe reduction of O2.
Keywords: bioinorganic chemistry; ferritin; iron; mineralization; tyrosyl radicals.
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