Reaction of O2 with a diiron protein generates a mixed-valent Fe2+/Fe3+ center and peroxide

Bradley, Justin M.; Svistunenko, Dimitri A.; Pullin, Jacob; Hill, Natalie; Stuart, Rhona K.; Palenik, Brian; Wilson, Michael T.; Hemmings, Andrew M.; Moore, Geoffrey R.; Le Brun, Nick E.

doi:10.1073/pnas.1809913116

Title: Reaction of O₂ with a diiron protein generates a mixed-valent Fe²⁺/Fe³⁺ center and peroxide

Journal Article · 04 February 2019 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1809913116 · OSTI ID:1513108

Bradley, Justin M.; Svistunenko, Dimitri A.; Pullin, Jacob; Hill, Natalie; Stuart, Rhona K.; Palenik, Brian; Wilson, Michael T.; Hemmings, Andrew M.; Moore, Geoffrey R.;

The gene encoding the cyanobacterial ferritin Syn Ftn is up-regulated in response to copper stress. Here, we show that, while Syn Ftn 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 O₂with the di-Fe²⁺center results in a direct, one-electron oxidation to a mixed-valent Fe²⁺/Fe³⁺form. Iron–O₂chemistry 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 O₂reduction, implying that ferroxidase centers function in pairs via long-range electron transfer through the protein resulting in reduction of O₂bound 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–O₂chemistry 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.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1513108

Report Number(s):: LLNL-JRNL--764177; 954137

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 6 Vol. 116; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

References (54)

Three Aromatic Residues are Required for Electron Transfer during Iron Mineralization in Bacterioferritin Bradley, Justin M.; Svistunenko, Dimitri A.; Lawson, Tamara L. Angewandte Chemie, Vol. 127, Issue 49 https://doi.org/10.1002/ange.201507486	journal	October 2015
The Firstμ(OH)-Bridged Model Complex for the Mixed-Valent FeIIFeIII Form of Hemerythrin Bossek, Ursula; Hummel, Helga; Weyhermüller, Thomas Angewandte Chemie International Edition in English, Vol. 34, Issue 2324 https://doi.org/10.1002/anie.199526421	journal	January 1996
Three Aromatic Residues are Required for Electron Transfer during Iron Mineralization in Bacterioferritin Bradley, Justin M.; Svistunenko, Dimitri A.; Lawson, Tamara L. Angewandte Chemie International Edition, Vol. 54, Issue 49 https://doi.org/10.1002/anie.201507486	journal	October 2015
A Conserved Tyrosine in Ferritin Is a Molecular Capacitor Ebrahimi, Kourosh Honarmand; Hagedoorn, Peter-Leon; Hagen, Wilfred R. ChemBioChem, Vol. 14, Issue 9 https://doi.org/10.1002/cbic.201300149	journal	June 2013
Correlating Structure with Function in Bacterial Multicomponent Monooxygenases and Related Diiron Proteins Sazinsky, Matthew H.; Lippard, Stephen J. ChemInform, Vol. 37, Issue 45 https://doi.org/10.1002/chin.200645275	journal	November 2006
The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe3+ and Zn2+ derivatives11Edited by R. Huber Stillman, T. J.; Hempstead, P. D.; Artymiuk, P. J. Journal of Molecular Biology, Vol. 307, Issue 2 https://doi.org/10.1006/jmbi.2001.4475	journal	March 2001
A highly thermostable ferritin from the hyperthermophilic archaeal anaerobe Pyrococcus furiosus Tatur, Jana; Hagedoorn, Peter-Leon; Overeijnder, Marieke L. Extremophiles, Vol. 10, Issue 2 https://doi.org/10.1007/s00792-005-0484-x	journal	December 2005
Mössbauer spectroscopic investigation of structure-function relations in ferritins Bauminger, Erika R.; Harrison, Pauline M.; Hechel, Daniel Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, Vol. 1118, Issue 1 https://doi.org/10.1016/0167-4838(91)90440-B	journal	December 1991
Ferritin, iron homeostasis, and oxidative damage1,2 1Guest Editor: Mario Comporti 2This article is part of a series of reviews on “Iron and Cellular Redox Status.” The full list of papers may be found on the homepage of the journal. Arosio, Paolo; Levi, Sonia Free Radical Biology and Medicine, Vol. 33, Issue 4 https://doi.org/10.1016/S0891-5849(02)00842-0	journal	August 2002
Ferritins and iron storage in plants Briat, Jean-François; Duc, Céline; Ravet, Karl Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1800, Issue 8 https://doi.org/10.1016/j.bbagen.2009.12.003	journal	August 2010
Iron core mineralisation in prokaryotic ferritins Le Brun, Nick E.; Crow, Allister; Murphy, Michael E. P. Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1800, Issue 8 https://doi.org/10.1016/j.bbagen.2010.04.002	journal	August 2010
Electron transfer in peptides and proteins Giese, Bernd; Graber, Michael; Cordes, Meike Current Opinion in Chemical Biology, Vol. 12, Issue 6 https://doi.org/10.1016/j.cbpa.2008.08.026	journal	December 2008
Diversity of Fe 2+ entry and oxidation in ferritins Bradley, Justin M.; Moore, Geoffrey R.; Le Brun, Nick E. Current Opinion in Chemical Biology, Vol. 37 https://doi.org/10.1016/j.cbpa.2017.02.027	journal	April 2017
Ferritins for chemistry and for life Theil, Elizabeth C.; Behera, Rabindra K.; Tosha, Takehiko Coordination Chemistry Reviews, Vol. 257, Issue 2 https://doi.org/10.1016/j.ccr.2012.05.013	journal	January 2013
A growing family of O2 activating dinuclear iron enzymes with key catalytic diiron(III)-peroxo intermediates: Biological systems and chemical models Trehoux, Alexandre; Mahy, Jean-Pierre; Avenier, Frédéric Coordination Chemistry Reviews, Vol. 322 https://doi.org/10.1016/j.ccr.2016.05.014	journal	September 2016
The dinuclear iron-oxo ferroxidase center of Pyrococcus furiosus ferritin is a stable prosthetic group with unexpectedly high reduction potentials Tatur, Jana; Hagen, Wilfred R. FEBS Letters, Vol. 579, Issue 21 https://doi.org/10.1016/j.febslet.2005.07.045	journal	August 2005
Dioxygen Activation by Nonheme Diiron Enzymes: Diverse Dioxygen Adducts, High-Valent Intermediates, and Related Model Complexes Jasniewski, Andrew J.; Que, Lawrence Chemical Reviews, Vol. 118, Issue 5 https://doi.org/10.1021/acs.chemrev.7b00457	journal	December 2017
Correlating Structure with Function in Bacterial Multicomponent Monooxygenases and Related Diiron Proteins Sazinsky, Matthew H.; Lippard, Stephen J. Accounts of Chemical Research, Vol. 39, Issue 8 https://doi.org/10.1021/ar030204v	journal	August 2006
EPR and ENDOR Evidence for a 1-His, Hydroxo-Bridged Mixed-Valent Diiron Site in Desulfovibrio vulgaris Rubrerythrin ^† Smoukov, Stoyan K.; Davydov, Roman M.; Doan, Peter E. Biochemistry, Vol. 42, Issue 20 https://doi.org/10.1021/bi0300027	journal	May 2003
A Coupled Dinuclear Iron Cluster that Is Perturbed by Substrate Binding in myo -Inositol Oxygenase ^† Xing, Gang; Hoffart, Lee M.; Diao, Yinghui Biochemistry, Vol. 45, Issue 17 https://doi.org/10.1021/bi0519607	journal	May 2006
Functionality of the Three-Site Ferroxidase Center of Escherichia coli Bacterial Ferritin (EcFtnA) Bou-Abdallah, F.; Yang, H.; Awomolo, A. Biochemistry, Vol. 53, Issue 3 https://doi.org/10.1021/bi401517f	journal	January 2014
Monitoring the Iron Status of the Ferroxidase Center of Escherichia coli Bacterioferritin Using Fluorescence Spectroscopy Lawson, Tamara L.; Crow, Allister; Lewin, Allison Biochemistry, Vol. 48, Issue 38 https://doi.org/10.1021/bi900869x	journal	September 2009
EPR Study of the Mixed-Valent Diiron Sites in Mouse and Herpes Simplex Virus Ribonucleotide Reductases. Effect of the Tyrosyl Radical on Structure and Reactivity of the Diferric Center ^† Davydov, Roman M.; Davydov, Albert; Ingemarson, Rolf Biochemistry, Vol. 36, Issue 30 https://doi.org/10.1021/bi9700375	journal	July 1997
Reaction Paths of Iron Oxidation and Hydrolysis in Horse Spleen and Recombinant Human Ferritins ^† Yang, Xiaoke; Chen-Barrett, Yu; Arosio, Paolo Biochemistry, Vol. 37, Issue 27 https://doi.org/10.1021/bi973128a	journal	July 1998
Direct Spectroscopic and Kinetic Evidence for the Involvement of a Peroxodiferric Intermediate during the Ferroxidase Reaction in Fast Ferritin Mineralization ^† Pereira, Alice S.; Small, William; Krebs, Carsten Biochemistry, Vol. 37, Issue 28 https://doi.org/10.1021/bi980847w	journal	July 1998
An EPR Study of the Dinuclear Iron Site in the Soluble Methane Monooxygenase from Methylococcus capsulatus (Bath) Reduced by One Electron at 77 K: The Effects of Component Interactions and the Binding of Small Molecules to the Diiron(III) Center ^† Davydov, Roman; Valentine, Ann M.; Komar-Panicucci, Sonja Biochemistry, Vol. 38, Issue 13 https://doi.org/10.1021/bi982391o	journal	March 1999
Unity in the Biochemistry of the Iron-Storage Proteins Ferritin and Bacterioferritin Honarmand Ebrahimi, Kourosh; Hagedoorn, Peter-Leon; Hagen, Wilfred R. Chemical Reviews, Vol. 115, Issue 1 https://doi.org/10.1021/cr5004908	journal	November 2014
Structural, EPR, and Mössbauer Characterization of (μ-Alkoxo)(μ-Carboxylato)Diiron(II,III) Model Complexes for the Active Sites of Mixed-Valent Diiron Enzymes Li, Feifei; Chakrabarti, Mrinmoy; Dong, Yanhong Inorganic Chemistry, Vol. 51, Issue 5 https://doi.org/10.1021/ic2021726	journal	February 2012
Reduction of the binuclear iron site in octameric methemerythrins. Characterizations of intermediates and a unifying reaction scheme Pearce, Linda L.; Kurtz, Donald M.; Xia, Yao Min Journal of the American Chemical Society, Vol. 109, Issue 24 https://doi.org/10.1021/ja00258a007	journal	November 1987
Compound ES of Dehaloperoxidase Decays via Two Alternative Pathways Depending on the Conformation of the Distal Histidine Thompson, Matthew K.; Franzen, Stefan; Ghiladi, Reza A. Journal of the American Chemical Society, Vol. 132, Issue 49 https://doi.org/10.1021/ja106620q	journal	December 2010
Structural Insights into the Ferroxidase Site of Ferritins from Higher Eukaryotes Bertini, Ivano; Lalli, Daniela; Mangani, Stefano Journal of the American Chemical Society, Vol. 134, Issue 14 https://doi.org/10.1021/ja210084n	journal	March 2012
The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement Honarmand Ebrahimi, Kourosh; Bill, Eckhard; Hagedoorn, Peter-Leon Nature Chemical Biology, Vol. 8, Issue 11 https://doi.org/10.1038/nchembio.1071	journal	September 2012
Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server Zheng, Heping; Chordia, Mahendra D.; Cooper, David R. Nature Protocols, Vol. 9, Issue 1 https://doi.org/10.1038/nprot.2013.172	journal	December 2013
Characterizing metal-binding sites in proteins with X-ray crystallography Handing, Katarzyna B.; Niedzialkowska, Ewa; Shabalin, Ivan G. Nature Protocols, Vol. 13, Issue 5 https://doi.org/10.1038/nprot.2018.018	journal	April 2018
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Studies of copper(ii)-binding to bacterioferritin and its effect on iron(ii) oxidationBased on the presentation given at Dalton Discussion No. 4, 10–13th January 2002, Kloster Banz, Germany. Baaghil, Suzanne; Thomson, Andrew J.; Moore, Geoffrey R. Journal of the Chemical Society, Dalton Transactions, Issue 5 https://doi.org/10.1039/b107288a	journal	January 2002
Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin Levi, S.; Yewdall, S. J.; Harrison, P. M. Biochemical Journal, Vol. 288, Issue 2 https://doi.org/10.1042/bj2880591	journal	December 1992
Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage reaction catalyzed by myo-inositol oxygenase Xing, G.; Diao, Y.; Hoffart, L. M. Proceedings of the National Academy of Sciences, Vol. 103, Issue 16 https://doi.org/10.1073/pnas.0508473103	journal	April 2006
The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity Macomber, L.; Imlay, J. A. Proceedings of the National Academy of Sciences, Vol. 106, Issue 20 https://doi.org/10.1073/pnas.0812808106	journal	May 2009
Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases Worsdorfer, B.; Lingaraju, M.; Yennawar, N. H. Proceedings of the National Academy of Sciences, Vol. 110, Issue 47 https://doi.org/10.1073/pnas.1315927110	journal	November 2013
Mechanism of Ferrous Iron Binding and Oxidation by Ferritin from a Pennate Diatom Pfaffen, Stephanie; Abdulqadir, Raz; Le Brun, Nick E. Journal of Biological Chemistry, Vol. 288, Issue 21 https://doi.org/10.1074/jbc.M113.454496	journal	April 2013
xia2 : an expert system for macromolecular crystallography data reduction Winter, G. Journal of Applied Crystallography, Vol. 43, Issue 1 https://doi.org/10.1107/S0021889809045701	journal	December 2009
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
An introduction to data reduction: space-group determination, scaling and intensity statistics Evans, Philip R. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S090744491003982X	journal	March 2011
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
Time-lapse anomalous X-ray diffraction shows how Fe ²⁺ substrate ions move through ferritin protein nanocages to oxidoreductase sites Pozzi, Cecilia; Di Pisa, Flavio; Lalli, Daniela Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 4 https://doi.org/10.1107/S1399004715002333	journal	March 2015
Iron binding to human heavy-chain ferritin Pozzi, Cecilia; Di Pisa, Flavio; Bernacchioni, Caterina Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 9 https://doi.org/10.1107/S1399004715013073	journal	August 2015
Functional distinctness in the exoproteomes of marine S ynechococcus : Exoproteomes of marine Christie-Oleza, Joseph A.; Armengaud, Jean; Guerin, Philippe Environmental Microbiology, Vol. 17, Issue 10 https://doi.org/10.1111/1462-2920.12822	journal	April 2015
Coastal Strains of Marine Synechococcus Species Exhibit Increased Tolerance to Copper Shock and a Distinctive Transcriptional Response Relative to Those of Open-Ocean Strains Stuart, R. K.; Dupont, C. L.; Johnson, D. A. Applied and Environmental Microbiology, Vol. 75, Issue 15 https://doi.org/10.1128/AEM.00271-09	journal	June 2009
Accelerated evolution associated with genome reduction in a free-living prokaryote Dufresne, Alexis; Garczarek, Laurence; Partensky, Frédéric Genome Biology, Vol. 6, Issue 2, p. R14 https://doi.org/10.1186/gb-2005-6-2-r14	journal	January 2005
A New Method of Identifying the Site of Tyrosyl Radicals in Proteins Svistunenko, Dimitri A.; Cooper, Chris E. Biophysical Journal, Vol. 87, Issue 1 https://doi.org/10.1529/biophysj.104.041046	journal	July 2004
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
Primary production of prochlorophytes, cyanobacteria, and eucaryotic ultraphytoplankton: Measurements from flow cytometric sorting Li, William K. W. Limnology and Oceanography, Vol. 39, Issue 1 https://doi.org/10.4319/lo.1994.39.1.0169	journal	January 1994

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
diiron protein
electron transfer
ferritin
iron
tyrosyl radical

Title: Reaction of O2 with a diiron protein generates a mixed-valent Fe2+/Fe3+ center and peroxide

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Title: Reaction of O₂ with a diiron protein generates a mixed-valent Fe²⁺/Fe³⁺ center and peroxide