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Reaction of O 2 with a diiron protein generates a mixed-valent Fe 2+ /Fe 3+ center and peroxide

DOI: 10.1073/pnas.1809913116 DOI Help

Authors: Justin M. Bradley (University of East Anglia) , Dimitri A. Svistunenko (University of Essex) , Jacob Pullin (University of Essex) , Natalie Hill (University of East Anglia) , Rhona K. Stuart (Scripps Institution of Oceanography, University of California) , Brian Palenik (Scripps Institution of Oceanography, University of California) , Michael T. Wilson (University of Essex) , Andrew M. Hemmings (University of East Anglia) , Geoffrey R. Moore (University of East Anglia) , Nick E. Le Brun (University of East Anglia)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 37

State: Published (Approved)
Published: January 2019
Diamond Proposal Number(s): 9475

Abstract: The gene encoding the cyanobacterial ferritin SynFtn is up-regulated in response to copper stress. Here, we show that, while SynFtn does not interact directly with copper, it is highly unusual in several ways. First, its catalytic diiron ferroxidase center is unlike those of all other characterized prokaryotic ferritins and instead resembles an animal H-chain ferritin center. Second, as demonstrated by kinetic, spectroscopic, and high-resolution X-ray crystallographic data, reaction of O2 with the di-Fe2+ center results in a direct, one-electron oxidation to a mixed-valent Fe2+/Fe3+ form. Iron–O2 chemistry of this type is currently unknown among the growing family of proteins that bind a diiron site within a four α-helical bundle in general and ferritins in particular. The mixed-valent form, which slowly oxidized to the more usual di-Fe3+ form, is an intermediate that is continually generated during mineralization. Peroxide, rather than superoxide, is shown to be the product of O2 reduction, implying that ferroxidase centers function in pairs via long-range electron transfer through the protein resulting in reduction of O2 bound at only one of the centers. We show that electron transfer is mediated by the transient formation of a radical on Tyr40, which lies ∼4 Å from the diiron center. As well as demonstrating an expansion of the iron–O2 chemistry known to occur in nature, these data are also highly relevant to the question of whether all ferritins mineralize iron via a common mechanism, providing unequivocal proof that they do not.

Journal Keywords: diiron protein; ferritin; iron; tyrosyl radical; electron transfer

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

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