A Short Fe-Fe Distance in Peroxodiferric Ferritin: Control of Fe Substrate Versus Cofactor Decay?

TLDR

Oxygen reactions at protein diiron sites are central to bioorganic synthesis and biomineralization, yet previously characterized μ‑1,2 peroxodiferric complexes exhibit Fe‑Fe separations of 3.1–4.0 Å. The authors report a 2.53‑Å Fe‑Fe distance in a ferritin μ‑1,2 peroxodiferric intermediate, indicating a triply bridged structure with a small Fe‑O‑O angle that promotes decay to H₂O₂ and diferric precursors rather than substrate oxidation, thereby explaining the dual substrate/cofactor role of diiron sites.

Abstract

The reaction of oxygen with protein diiron sites is important in bioorganic syntheses and biomineralization. An unusually short Fe-Fe distance of 2.53 angstroms was found in the diiron (μ-1,2 peroxodiferric) intermediate that forms in the early steps of ferritin biomineralization. This distance suggests the presence of a unique triply bridged structure. The Fe-Fe distances in the μ-1,2 peroxodiferric complexes that were characterized previously are much longer (3.1 to 4.0 angstroms). The 2.53 angstrom Fe-Fe distance requires a small Fe-O-O angle (∼106° to 107°). This geometry should favor decay of the peroxodiferric complex by the release of H 2 O 2 and μ-oxo or μ-hydroxo diferric biomineral precursors rather than by oxidation of the organic substrate. Geometrical differences may thus explain how diiron sites can function either as a substrate (in ferritin biomineralization) or as a cofactor (in O 2 activation).