title: Iron and hydrogen peroxide detoxification properties of DNA-binding protein from starved cells. A ferritin-like DNA-binding protein of Escherichia coli.
abstract: The DNA-binding proteins from starved cells (Dps) are a family of proteins induced in microorganisms by oxidative or nutritional stress. Escherichia coli Dps, a structural analog of the 12-subunit Listeria innocua ferritin, binds and protects DNA against oxidative damage mediated by H(2)O(2). Dps is shown to be a Fe-binding and storage protein where Fe(II) oxidation is most effectively accomplished by H(2)O(2) rather than by O(2) as in ferritins. Two Fe(2+) ions bind at each of the 12 putative dinuclear ferroxidase sites (P(Z)) in the protein according to the equation, 2Fe(2+) + P(Z) --> [(Fe(II)(2)-P](FS)(Z+2) + 2H(+). The ferroxidase site (FS) bound iron is then oxidized according to the equation, [(Fe(II)(2)-P](FS)(Z+2) + H(2)O(2) + H(2)O --> [Fe(III)(2)O(2)(OH)-P](FS)(Z-1) + 3H(+), where two Fe(II) are oxidized per H(2)O(2) reduced, thus avoiding hydroxyl radical production through Fenton chemistry. Dps acquires a ferric core of approximately 500 Fe(III) according to the mineralization equation, 2Fe(2+) + H(2)O(2) + 2H(2)O --> 2Fe(III)OOH((core)) + 4H(+), again with a 2 Fe(II)/H(2)O(2) stoichiometry. The protein forms a similar ferric core with O(2) as the oxidant, albeit at a slower rate. In the absence of H(2)O(2) and O(2), Dps forms a ferrous core of approximately 400 Fe(II) by the reaction Fe(2+) + H(2)O + Cl(-) --> Fe(II)OHCl((core)) + H(+). The ferrous core also undergoes oxidation with a stoichiometry of 2 Fe(II)/H(2)O(2). Spin trapping experiments demonstrate that Dps greatly attenuates hydroxyl radical production during Fe(II) oxidation by H(2)O(2). These results and in vitro DNA damage assays indicate that the protective effect of Dps on DNA most likely is exerted through a dual action, the physical association with DNA and the ability to nullify the toxic combination of Fe(II) and H(2)O(2). In the latter process a hydrous ferric oxide mineral core is produced within the protein, thus avoiding oxidative damage mediated by Fenton chemistry.
authors.affiliation: Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Zhao
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ceci
authors.forename: Andrea
authors.initials: A
authors.lastname: Ilari
authors.forename: Laura
authors.initials: L
authors.lastname: Giangiacomo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Laue
authors.forename: Emilia
authors.initials: E
authors.lastname: Chiancone
authors.forename: N Dennis
authors.initials: ND
authors.lastname: Chasteen
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002570:Ceruloplasmin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000493:pharmacokinetics* / Q000494:pharmacology; D008658:Inactivation, Metabolic; D007501:Iron / Q000493:pharmacokinetics* / Q000494:pharmacology; D007700:Kinetics; D010084:Oxidation-Reduction
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron; D002570:Ceruloplasmin