reactions are anaerobic and can involve uncharacterized intermediates with UV
absorption properties similar to differic peroxo of maxi-ferritins (Liu et al. 2006).
2.3.3 Step iii. Release of Differric Oxo Mineral Precursors
from Active Sites
Release of the Fe(III)O product of ferritin catalysis varies among ferritins. In BFR
and most Dps, the ferric oxo product is thought to be released directly into the
protein cavity, because of the proximity of the active sites to the cavity surface. In
BFR, and possibly Pyrococcus furiosus ferritins, where two iron atoms are
cofactors, the active sites are proposed to dominate dioxygen reduction while
ferrous oxidation occurs in the cavity on protein or mineral surfaces with the
released electron used to reduce the cofactor ferric iron and recycle the catalytic
center (Le Brun et al. 2010). However, the properties of various ferric species
remain uncharacterized. In eukaryotic ferritins, where the differic peroxo intermediate results from dioxygen and ferrous, the reactions produced is a differic oxo
complex and multimeric ferric oxo complexes (Jameson et al. 2002). Even though
the active sites in eukaryotic ferritin protein cages, like those in prokaryotic ferritins,
have direct access to the internal cavity (Tosha et al. 2008), recent NMR evidence
reveals that the differic oxo products of ferritin protein catalysts remain inside the
protein cage and move along an interior trajectory of 20 A ˚ through the protein cage
to the cavity surface. During passage through the protein, reactions occur among the
ferric oxo products of multiple catalytic cycles (Turano et al. 2010) (Fig. 2.4),
leading to the formation of multinuclear ferric oxide complexes inside the protein
cage itself. Whether this feature is an evolutionary advance in eukaryotic ferritins or
a property yet to be detected in prokaryotic and archaeal ferritins, remains unknown.
2.3.4 Step iv. Nucleation and Mineralization
Nucleation and mineralization in prokaryotic ferritins, BFR, and mini-ferritins is
considered to be essentially inorganic hydrolytic chemistry of ferric oxo complexes
where the effective concentration of iron is increased by the volume of the cavity.
Ferrous ions are propelled into the cavity from the exterior of the protein cages by
high-affinity binding sites (active sites) that harvest ferrous ions moving into the
cage through pores lined with negatively charged amino acids (Theil et al. 2008;
Bellapadrona et al. 2009); in recombinant ferritins with only animal L subunits and
no catalytic sites, oxidation and mineralization is ~1,000 times slower. Pores with
negative charges are formed around the threefold axes in both mini-ferritins and
maxi-ferritins; highly conserved residues control pore folding/unfolding which
influences iron mineral dissolution more than mineral synthesis.
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
39
absorption properties similar to differic peroxo of maxi-ferritins (Liu et al. 2006).
2.3.3 Step iii. Release of Differric Oxo Mineral Precursors
from Active Sites
Release of the Fe(III)O product of ferritin catalysis varies among ferritins. In BFR
and most Dps, the ferric oxo product is thought to be released directly into the
protein cavity, because of the proximity of the active sites to the cavity surface. In
BFR, and possibly Pyrococcus furiosus ferritins, where two iron atoms are
cofactors, the active sites are proposed to dominate dioxygen reduction while
ferrous oxidation occurs in the cavity on protein or mineral surfaces with the
released electron used to reduce the cofactor ferric iron and recycle the catalytic
center (Le Brun et al. 2010). However, the properties of various ferric species
remain uncharacterized. In eukaryotic ferritins, where the differic peroxo intermediate results from dioxygen and ferrous, the reactions produced is a differic oxo
complex and multimeric ferric oxo complexes (Jameson et al. 2002). Even though
the active sites in eukaryotic ferritin protein cages, like those in prokaryotic ferritins,
have direct access to the internal cavity (Tosha et al. 2008), recent NMR evidence
reveals that the differic oxo products of ferritin protein catalysts remain inside the
protein cage and move along an interior trajectory of 20 A ˚ through the protein cage
to the cavity surface. During passage through the protein, reactions occur among the
ferric oxo products of multiple catalytic cycles (Turano et al. 2010) (Fig. 2.4),
leading to the formation of multinuclear ferric oxide complexes inside the protein
cage itself. Whether this feature is an evolutionary advance in eukaryotic ferritins or
a property yet to be detected in prokaryotic and archaeal ferritins, remains unknown.
2.3.4 Step iv. Nucleation and Mineralization
Nucleation and mineralization in prokaryotic ferritins, BFR, and mini-ferritins is
considered to be essentially inorganic hydrolytic chemistry of ferric oxo complexes
where the effective concentration of iron is increased by the volume of the cavity.
Ferrous ions are propelled into the cavity from the exterior of the protein cages by
high-affinity binding sites (active sites) that harvest ferrous ions moving into the
cage through pores lined with negatively charged amino acids (Theil et al. 2008;
Bellapadrona et al. 2009); in recombinant ferritins with only animal L subunits and
no catalytic sites, oxidation and mineralization is ~1,000 times slower. Pores with
negative charges are formed around the threefold axes in both mini-ferritins and
maxi-ferritins; highly conserved residues control pore folding/unfolding which
influences iron mineral dissolution more than mineral synthesis.
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
39