title: Three Aromatic Residues are Required for Electron Transfer during Iron Mineralization in Bacterioferritin.
abstract: 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.
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK).
authors.forename: Justin M
authors.initials: JM
authors.lastname: Bradley
authors.affiliation: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ (UK).
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Svistunenko
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK).
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lawson
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK).|School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich NR4 7TJ (UK).
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hemmings
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK).
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Moore
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ (UK). n.le-brun@uea.ac.uk.
authors.forename: Nick E
authors.initials: NE
authors.lastname: Le Brun
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003573:Cytochrome b Group / Q000737:chemistry* / Q000378:metabolism*; D004579:Electron Transport; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism*; D007501:Iron / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular
chemical_list: D001426:Bacterial Proteins; D003573:Cytochrome b Group; D005293:Ferritins; C018032:bacterioferritin; D007501:Iron
keywords: bioinorganic chemistry; ferritin; iron; mineralization; tyrosyl radicals