mu-1,2-Peroxobridged di-iron(III) dimer formation in human H-chain ferritin.
Biomineralization of the ferritin iron core involves a complex series of events in which H(2)O(2) is produced during iron oxidation by O(2) at a dinuclear centre, the 'ferroxidase site', located on the H-subunit of mammalian proteins. Rapid-freeze quench Mössbauer spectroscopy was used to probe the early events of iron oxidation and mineralization in recombinant human ferritin containing 24 H-subunits. The spectra reveal that a mu-1,2-peroxodiFe(III) intermediate (species P) with Mössbauer parameters delta (isomer shift)=0.58 mm/s and DeltaE(Q) (quadrupole splitting)=1.07 mm/s at 4.2 K is formed within 50 ms of mixing Fe(II) with the apoprotein. This intermediate accounts for almost all of the iron in the sample at 160 ms. It subsequently decays within 10 s to form a mu-oxodiFe(III)-protein complex (species D), which partially vacates the ferroxidase sites of the protein to generate Fe(III) clusters (species C) at a reaction time of 10 min. The intermediate peroxodiFe(III) complex does not decay under O(2)-limiting conditions, an observation suggesting inhibition of decay by unreacted Fe(II), or a possible role for O(2) in ferritin biomineralization in addition to that of direct oxidation of iron(II).
Bou-Abdallah
Fadi
F
Department of Chemistry, University of New Hampshire, Durham, NH 03824, USA.
Papaefthymiou
Georgia C
GC
Scheswohl
Danielle M
DM
Stanga
Sean D
SD
Arosio
Paolo
P
Chasteen
N Dennis
ND
D001669:Biochemical Phenomena; D001671:Biochemistry; D019281:Dimerization; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D008956:Models, Chemical; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013057:Spectrum Analysis; D013696:Temperature; D013816:Thermodynamics
D011994:Recombinant Proteins; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron