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Variable coordination geometries at the diiron(II) active site of ribonucleotide reductase R2.

Voegtli WC, Sommerhalter M, Saleh L, Baldwin J, Bollinger JM, Rosenzweig AC
J Am Chem Soc 125 15822-30 (2003)
Related entries: 1piy, 1piz, 1pj0, 1pm2, 1r65

Cited: 25 times
EuropePMC logo PMID: 14677973

Abstract

The R2 subunit of Escherichia coli ribonucleotide reductase contains a dinuclear iron center that generates a catalytically essential stable tyrosyl radical by one electron oxidation of a nearby tyrosine residue. After acquisition of Fe(II) ions by the apo protein, the resulting diiron(II) center reacts with O(2) to initiate formation of the radical. Knowledge of the structure of the reactant diiron(II) form of R2 is a prerequisite for a detailed understanding of the O(2) activation mechanism. Whereas kinetic and spectroscopic studies of the reaction have generally been conducted at pH 7.6 with reactant produced by the addition of Fe(II) ions to the apo protein, the available crystal structures of diferrous R2 have been obtained by chemical or photoreduction of the oxidized diiron(III) protein at pH 5-6. To address this discrepancy, we have generated the diiron(II) states of wildtype R2 (R2-wt), R2-D84E, and R2-D84E/W48F by infusion of Fe(II) ions into crystals of the apo proteins at neutral pH. The structures of diferrous R2-wt and R2-D48E determined from these crystals reveal diiron(II) centers with active site geometries that differ significantly from those observed in either chemically or photoreduced crystals. Structures of R2-wt and R2-D48E/W48F determined at both neutral and low pH are very similar, suggesting that the differences are not due solely to pH effects. The structures of these "ferrous soaked" forms are more consistent with circular dichroism (CD) and magnetic circular dichroism (MCD) spectroscopic data and provide alternate starting points for consideration of possible O(2) activation mechanisms.

Reviews citing this publication (7)

  1. Class I ribonucleotide reductases: metallocofactor assembly and repair in vitro and in vivo. Cotruvo JA, Stubbe J. Annu Rev Biochem 80 733-767 (2011)
  2. Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: the class I ribonucleotide reductases as a case study. Cotruvo JA, Stubbe J. Metallomics 4 1020-1036 (2012)
  3. myo-Inositol oxygenase: a radical new pathway for O(2) and C-H activation at a nonheme diiron cluster. Bollinger JM, Diao Y, Matthews ML, Xing G, Krebs C. Dalton Trans 905-914 (2009)
  4. The periodic table of ribonucleotide reductases. Ruskoski TB, Boal AK. J Biol Chem 297 101137 (2021)
  5. Assembly of nonheme Mn/Fe active sites in heterodinuclear metalloproteins. Griese JJ, Srinivas V, Högbom M. J Biol Inorg Chem 19 759-774 (2014)
  6. Crystallographic evidence for dioxygen interactions with iron proteins. Carrondo MA, Bento I, Matias PM, Lindley PF. J Biol Inorg Chem 12 429-442 (2007)
  7. Why is manganese so valuable to bacterial pathogens? Čapek J, Večerek B. Front Cell Infect Microbiol 13 943390 (2023)

Articles citing this publication (18)

  1. Structural basis for activation of class Ib ribonucleotide reductase. Boal AK, Cotruvo JA, Stubbe J, Rosenzweig AC. Science 329 1526-1530 (2010)
  2. NrdI essentiality for class Ib ribonucleotide reduction in Streptococcus pyogenes. Roca I, Torrents E, Sahlin M, Gibert I, Sjöberg BM. J Bacteriol 190 4849-4858 (2008)
  3. Crystal structural studies of changes in the native dinuclear iron center of ribonucleotide reductase protein R2 from mouse. Strand KR, Karlsen S, Kolberg M, Røhr AK, Görbitz CH, Andersson KK. J Biol Chem 279 46794-46801 (2004)
  4. Insights into the nitric oxide reductase mechanism of flavodiiron proteins from a flavin-free enzyme. Hayashi T, Caranto JD, Wampler DA, Kurtz DM, Moënne-Loccoz P. Biochemistry 49 7040-7049 (2010)
  5. Effects of zinc on particulate methane monooxygenase activity and structure. Sirajuddin S, Barupala D, Helling S, Marcus K, Stemmler TL, Rosenzweig AC. J Biol Chem 289 21782-21794 (2014)
  6. Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical. Blaesi EJ, Palowitch GM, Hu K, Kim AJ, Rose HR, Alapati R, Lougee MG, Kim HJ, Taguchi AT, Tan KO, Laremore TN, Griffin RG, Krebs C, Matthews ML, Silakov A, Bollinger JM, Allen BD, Boal AK. Proc Natl Acad Sci U S A 115 10022-10027 (2018)
  7. Structural basis for assembly of the Mn(IV)/Fe(III) cofactor in the class Ic ribonucleotide reductase from Chlamydia trachomatis. Dassama LM, Krebs C, Bollinger JM, Rosenzweig AC, Boal AK. Biochemistry 52 6424-6436 (2013)
  8. Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class I Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor. Rose HR, Ghosh MK, Maggiolo AO, Pollock CJ, Blaesi EJ, Hajj V, Wei Y, Rajakovich LJ, Chang WC, Han Y, Hajj M, Krebs C, Silakov A, Pandelia ME, Bollinger JM, Boal AK. Biochemistry 57 2679-2693 (2018)
  9. The dimanganese(II) site of Bacillus subtilis class Ib ribonucleotide reductase. Boal AK, Cotruvo JA, Stubbe J, Rosenzweig AC. Biochemistry 51 3861-3871 (2012)
  10. Rapid X-ray photoreduction of dimetal-oxygen cofactors in ribonucleotide reductase. Sigfridsson KGV, Chernev P, Leidel N, Popović-Bijelić A, Gräslund A, Haumann M. J Biol Chem 288 9648-9661 (2013)
  11. Characterization of NO adducts of the diiron center in protein R2 of Escherichia coli ribonucleotide reductase and site-directed variants; implications for the O2 activation mechanism. Lu S, Libby E, Saleh L, Xing G, Bollinger JM, Moënne-Loccoz P. J Biol Inorg Chem 9 818-827 (2004)
  12. Structural Basis for Oxygen Activation at a Heterodinuclear Manganese/Iron Cofactor. Griese JJ, Kositzki R, Schrapers P, Branca RM, Nordström A, Lehtiö J, Haumann M, Högbom M. J Biol Chem 290 25254-25272 (2015)
  13. The structure of a designed diiron(III) protein: implications for cofactor stabilization and catalysis. Wade H, Stayrook SE, Degrado WF. Angew Chem Int Ed Engl 45 4951-4954 (2006)
  14. Redox-linked changes to the hydrogen-bonding network of ribonucleotide reductase β2. Offenbacher AR, Minnihan EC, Stubbe J, Barry BA. J Am Chem Soc 135 6380-6383 (2013)
  15. Structure and assembly of the diiron cofactor in the heme-oxygenase-like domain of the N-nitrosourea-producing enzyme SznF. McBride MJ, Pope SR, Hu K, Okafor CD, Balskus EP, Bollinger JM, Boal AK. Proc Natl Acad Sci U S A 118 e2015931118 (2021)
  16. Perturbations of aromatic amino acids are associated with iron cluster assembly in ribonucleotide reductase. Offenbacher AR, Chen J, Barry BA. J Am Chem Soc 133 6978-6988 (2011)
  17. Nuclear resonance vibrational spectroscopy and DFT study of peroxo-bridged biferric complexes: structural insight into peroxo intermediates of binuclear non-heme iron enzymes. Park K, Tsugawa T, Furutachi H, Kwak Y, Liu LV, Wong SD, Yoda Y, Kobayashi Y, Saito M, Kurokuzu M, Seto M, Suzuki M, Solomon EI. Angew Chem Int Ed Engl 52 1294-1298 (2013)
  18. Spectroscopic studies of single and double variants of M ferritin: lack of conversion of a biferrous substrate site into a cofactor site for O2 activation. Kwak Y, Schwartz JK, Haldar S, Behera RK, Tosha T, Theil EC, Solomon EI. Biochemistry 53 473-482 (2014)


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