A Conserved Tyrosine in Ferritin Is a Molecular Capacitor

A highly conserved tyrosine residue of unknown function is present in the vicinity of the di‐iron catalytic center of the ubiquitous iron‐storage protein ferritin. The di‐iron center with a gateway Fe^II/Fe^III‐binding site nearby provides the vital iron‐storage mechanism of the protein. It is believed that, in eukaryotic ferritin, this center catalyzes simultaneous oxidation of two Fe^II ions, whereas in microbial ferritin it catalyzes simultaneous oxidation of three Fe^II ions. To understand the role of the conserved tyrosine, we studied the intermediates and products that are formed during catalysis of Fe^II oxidation in the di‐iron catalytic centers of the hyperthermophilic archaeal Pyrococcus furiosus ferritin and of eukaryotic human H ferritin. Based on our spectroscopic studies and modeling, we propose a merger of the models for eukaryotic and bacterial ferritin into a common mechanism of Fe^II oxidation in which the conserved tyrosine acts as a single‐electron molecular capacitor to facilitate oxidation of Fe^II.