A manganese(IV)/iron(IV) intermediate in assembly of the manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase

Wei Jiang, Lee M. Hoffart, Carsten Krebs, Joseph M. Bollinger, Jr.

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We recently showed that the class Ic ribonucleotide reductase from the human pathogen Chlamydia trachomatis uses a MnIV/FeIII cofactor to generate protein and substrate radicals in its catalytic mechanism [Jiang, W., Yun, D., Saleh, L., Barr, E. W., Xing, G., Hoffart, L. M., Maslak, M.-A., Krebs, C., and Bollinger, J. M., Jr. (2007) Science 316, 1188-1191]. Here, we have dissected the mechanism of formation of this novel heterobinuclear redox cofactor from the MnII/FeII cluster and O 2. An intermediate with a g = 2 EPR signal that shows hyperfine coupling to both 55Mn and 57Fe accumulates almost quantitatively in a second-order reaction between O2 and the reduced R2 complex. The otherwise slow decay of the intermediate to the active Mn IV/FeIII-R2 complex is accelerated by the presence of the one-electron reductant, ascorbate, implying that the intermediate is more oxidized than MnIV/FeIII. Mössbauer spectra show that the intermediate contains a high-spin FeIV center. Its chemical and spectroscopic properties establish that the intermediate is a Mn IV/FeIV-R2 complex with an S = 1/2 electronic ground state arising from antiferromagnetic coupling between the MnIV (S Mn = 3/2) and high-spin FeIV (SFe = 2) sites.

Original languageEnglish (US)
Pages (from-to)8709-8716
Number of pages8
JournalBiochemistry
Volume46
Issue number30
DOIs
StatePublished - Jul 31 2007

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Ribonucleotide Reductases
Chlamydia trachomatis
Reducing Agents
Pathogens
Manganese
Ground state
Oxidation-Reduction
Paramagnetic resonance
Iron
Electrons
Substrates
Proteins
myristoylmethionine
ferryl iron

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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title = "A manganese(IV)/iron(IV) intermediate in assembly of the manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase",
abstract = "We recently showed that the class Ic ribonucleotide reductase from the human pathogen Chlamydia trachomatis uses a MnIV/FeIII cofactor to generate protein and substrate radicals in its catalytic mechanism [Jiang, W., Yun, D., Saleh, L., Barr, E. W., Xing, G., Hoffart, L. M., Maslak, M.-A., Krebs, C., and Bollinger, J. M., Jr. (2007) Science 316, 1188-1191]. Here, we have dissected the mechanism of formation of this novel heterobinuclear redox cofactor from the MnII/FeII cluster and O 2. An intermediate with a g = 2 EPR signal that shows hyperfine coupling to both 55Mn and 57Fe accumulates almost quantitatively in a second-order reaction between O2 and the reduced R2 complex. The otherwise slow decay of the intermediate to the active Mn IV/FeIII-R2 complex is accelerated by the presence of the one-electron reductant, ascorbate, implying that the intermediate is more oxidized than MnIV/FeIII. M{\"o}ssbauer spectra show that the intermediate contains a high-spin FeIV center. Its chemical and spectroscopic properties establish that the intermediate is a Mn IV/FeIV-R2 complex with an S = 1/2 electronic ground state arising from antiferromagnetic coupling between the MnIV (S Mn = 3/2) and high-spin FeIV (SFe = 2) sites.",
author = "Wei Jiang and Hoffart, {Lee M.} and Carsten Krebs and {Bollinger, Jr.}, {Joseph M.}",
year = "2007",
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A manganese(IV)/iron(IV) intermediate in assembly of the manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase. / Jiang, Wei; Hoffart, Lee M.; Krebs, Carsten; Bollinger, Jr., Joseph M.

In: Biochemistry, Vol. 46, No. 30, 31.07.2007, p. 8709-8716.

Research output: Contribution to journalArticle

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T1 - A manganese(IV)/iron(IV) intermediate in assembly of the manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase

AU - Jiang, Wei

AU - Hoffart, Lee M.

AU - Krebs, Carsten

AU - Bollinger, Jr., Joseph M.

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AB - We recently showed that the class Ic ribonucleotide reductase from the human pathogen Chlamydia trachomatis uses a MnIV/FeIII cofactor to generate protein and substrate radicals in its catalytic mechanism [Jiang, W., Yun, D., Saleh, L., Barr, E. W., Xing, G., Hoffart, L. M., Maslak, M.-A., Krebs, C., and Bollinger, J. M., Jr. (2007) Science 316, 1188-1191]. Here, we have dissected the mechanism of formation of this novel heterobinuclear redox cofactor from the MnII/FeII cluster and O 2. An intermediate with a g = 2 EPR signal that shows hyperfine coupling to both 55Mn and 57Fe accumulates almost quantitatively in a second-order reaction between O2 and the reduced R2 complex. The otherwise slow decay of the intermediate to the active Mn IV/FeIII-R2 complex is accelerated by the presence of the one-electron reductant, ascorbate, implying that the intermediate is more oxidized than MnIV/FeIII. Mössbauer spectra show that the intermediate contains a high-spin FeIV center. Its chemical and spectroscopic properties establish that the intermediate is a Mn IV/FeIV-R2 complex with an S = 1/2 electronic ground state arising from antiferromagnetic coupling between the MnIV (S Mn = 3/2) and high-spin FeIV (SFe = 2) sites.

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