A coupled dinuclear iron cluster that is perturbed by substrate binding in myo-inositol oxygenase

Gang Xing, Lee M. Hoffart, Yinghui Diao, Kumble Sandeep Prabhu, Ryan J. Arner, C. Channa Reddy, Carsten Krebs, Joseph M. Bollinger, Jr.

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

myo-Inositol oxygenase (MIOX) uses iron as its cofactor and dioxygen as its cosubstrate to effect the unique, ring-cleaving, four-electron oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate to D-glucuronate. The nature of the iron cofactor and its interaction with the substrate, myo-inositol (MI), have been probed by electron paramagnetic resonance (EPR) and Mössbauer spectroscopies. The data demonstrate the formation of an antiferromagnetically coupled, high-spin diiron(III/III) cluster upon treatment of solutions of Fe(II) and MIOX with excess O2 or H2O2 and the formation of an antiferromagnetically coupled, valence-localized, high-spin diiron(II/III) cluster upon treatment with either limiting O2 or excess O2 in the presence of a mild reductant (e.g., ascorbate). Marked changes to the spectra of both redox forms upon addition of MI and analogy to changes induced by binding of phosphate to the diiron(II/III) cluster of the protein phosphatase, uteroferrin, suggest that MI coordinates directly to the diiron cluster, most likely in a bridging mode. The addition of MIOX to the growing family of non-heme diiron oxygenases expands the catalytic range of the family beyond the two-electron oxidation (hydroxylation and dehydrogenation) reactions catalyzed by its more extensively studied members such as methane monooxygenase and stearoyl acyl carrier protein Δ9-desaturase.

Original languageEnglish (US)
Pages (from-to)5393-5401
Number of pages9
JournalBiochemistry
Volume45
Issue number17
DOIs
StatePublished - May 2 2006

Fingerprint

Inositol Oxygenase
Inositol
acyl-(acyl-carrier-protein)desaturase
Iron
methane monooxygenase
Substrates
Electrons
Acyl Carrier Protein
Oxidation
Glucuronic Acid
Oxygenases
Hydroxylation
Phosphoprotein Phosphatases
Reducing Agents
Electron Spin Resonance Spectroscopy
Dehydrogenation
Oxidation-Reduction
Paramagnetic resonance
Spectrum Analysis
Phosphates

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Xing, Gang ; Hoffart, Lee M. ; Diao, Yinghui ; Prabhu, Kumble Sandeep ; Arner, Ryan J. ; Reddy, C. Channa ; Krebs, Carsten ; Bollinger, Jr., Joseph M. / A coupled dinuclear iron cluster that is perturbed by substrate binding in myo-inositol oxygenase. In: Biochemistry. 2006 ; Vol. 45, No. 17. pp. 5393-5401.
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abstract = "myo-Inositol oxygenase (MIOX) uses iron as its cofactor and dioxygen as its cosubstrate to effect the unique, ring-cleaving, four-electron oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate to D-glucuronate. The nature of the iron cofactor and its interaction with the substrate, myo-inositol (MI), have been probed by electron paramagnetic resonance (EPR) and M{\"o}ssbauer spectroscopies. The data demonstrate the formation of an antiferromagnetically coupled, high-spin diiron(III/III) cluster upon treatment of solutions of Fe(II) and MIOX with excess O2 or H2O2 and the formation of an antiferromagnetically coupled, valence-localized, high-spin diiron(II/III) cluster upon treatment with either limiting O2 or excess O2 in the presence of a mild reductant (e.g., ascorbate). Marked changes to the spectra of both redox forms upon addition of MI and analogy to changes induced by binding of phosphate to the diiron(II/III) cluster of the protein phosphatase, uteroferrin, suggest that MI coordinates directly to the diiron cluster, most likely in a bridging mode. The addition of MIOX to the growing family of non-heme diiron oxygenases expands the catalytic range of the family beyond the two-electron oxidation (hydroxylation and dehydrogenation) reactions catalyzed by its more extensively studied members such as methane monooxygenase and stearoyl acyl carrier protein Δ9-desaturase.",
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A coupled dinuclear iron cluster that is perturbed by substrate binding in myo-inositol oxygenase. / Xing, Gang; Hoffart, Lee M.; Diao, Yinghui; Prabhu, Kumble Sandeep; Arner, Ryan J.; Reddy, C. Channa; Krebs, Carsten; Bollinger, Jr., Joseph M.

In: Biochemistry, Vol. 45, No. 17, 02.05.2006, p. 5393-5401.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A coupled dinuclear iron cluster that is perturbed by substrate binding in myo-inositol oxygenase

AU - Xing, Gang

AU - Hoffart, Lee M.

AU - Diao, Yinghui

AU - Prabhu, Kumble Sandeep

AU - Arner, Ryan J.

AU - Reddy, C. Channa

AU - Krebs, Carsten

AU - Bollinger, Jr., Joseph M.

PY - 2006/5/2

Y1 - 2006/5/2

N2 - myo-Inositol oxygenase (MIOX) uses iron as its cofactor and dioxygen as its cosubstrate to effect the unique, ring-cleaving, four-electron oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate to D-glucuronate. The nature of the iron cofactor and its interaction with the substrate, myo-inositol (MI), have been probed by electron paramagnetic resonance (EPR) and Mössbauer spectroscopies. The data demonstrate the formation of an antiferromagnetically coupled, high-spin diiron(III/III) cluster upon treatment of solutions of Fe(II) and MIOX with excess O2 or H2O2 and the formation of an antiferromagnetically coupled, valence-localized, high-spin diiron(II/III) cluster upon treatment with either limiting O2 or excess O2 in the presence of a mild reductant (e.g., ascorbate). Marked changes to the spectra of both redox forms upon addition of MI and analogy to changes induced by binding of phosphate to the diiron(II/III) cluster of the protein phosphatase, uteroferrin, suggest that MI coordinates directly to the diiron cluster, most likely in a bridging mode. The addition of MIOX to the growing family of non-heme diiron oxygenases expands the catalytic range of the family beyond the two-electron oxidation (hydroxylation and dehydrogenation) reactions catalyzed by its more extensively studied members such as methane monooxygenase and stearoyl acyl carrier protein Δ9-desaturase.

AB - myo-Inositol oxygenase (MIOX) uses iron as its cofactor and dioxygen as its cosubstrate to effect the unique, ring-cleaving, four-electron oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate to D-glucuronate. The nature of the iron cofactor and its interaction with the substrate, myo-inositol (MI), have been probed by electron paramagnetic resonance (EPR) and Mössbauer spectroscopies. The data demonstrate the formation of an antiferromagnetically coupled, high-spin diiron(III/III) cluster upon treatment of solutions of Fe(II) and MIOX with excess O2 or H2O2 and the formation of an antiferromagnetically coupled, valence-localized, high-spin diiron(II/III) cluster upon treatment with either limiting O2 or excess O2 in the presence of a mild reductant (e.g., ascorbate). Marked changes to the spectra of both redox forms upon addition of MI and analogy to changes induced by binding of phosphate to the diiron(II/III) cluster of the protein phosphatase, uteroferrin, suggest that MI coordinates directly to the diiron cluster, most likely in a bridging mode. The addition of MIOX to the growing family of non-heme diiron oxygenases expands the catalytic range of the family beyond the two-electron oxidation (hydroxylation and dehydrogenation) reactions catalyzed by its more extensively studied members such as methane monooxygenase and stearoyl acyl carrier protein Δ9-desaturase.

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