Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class i Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor

Hannah R. Rose, Manas K. Ghosh, Ailiena O. Maggiolo, Christopher J. Pollock, Elizabeth J. Blaesi, Viviane Hajj, Yifeng Wei, Lauren J. Rajakovich, Wei Chen Chang, Yilin Han, Mariana Hajj, Carsten Krebs, Alexey Silakov, Maria Eirini Pandelia, Joseph M. Bollinger, Jr., Amie Kathleen Boal

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae (Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2 -) for activation, but it does not require the O2 --supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive "met" (III/III) forms seen with I(a-c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O2 - to the Mn2 II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.

Original languageEnglish (US)
Pages (from-to)2679-2693
Number of pages15
JournalBiochemistry
Volume57
Issue number18
DOIs
StatePublished - May 8 2018

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Flavobacterium
Ribonucleotide Reductases
Superoxides
Chemical activation
Proteins
Flavoproteins
Electrons
Reducing Agents
Scavenging
Ferritins
Manganese
Oxidants
Tyrosine
Hydrogen bonds
Hydrogen
Catalytic Domain

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Rose, Hannah R. ; Ghosh, Manas K. ; Maggiolo, Ailiena O. ; Pollock, Christopher J. ; Blaesi, Elizabeth J. ; Hajj, Viviane ; Wei, Yifeng ; Rajakovich, Lauren J. ; Chang, Wei Chen ; Han, Yilin ; Hajj, Mariana ; Krebs, Carsten ; Silakov, Alexey ; Pandelia, Maria Eirini ; Bollinger, Jr., Joseph M. ; Boal, Amie Kathleen. / Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class i Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor. In: Biochemistry. 2018 ; Vol. 57, No. 18. pp. 2679-2693.
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abstract = "A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae (Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2 -) for activation, but it does not require the O2 --supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive {"}met{"} (III/III) forms seen with I(a-c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O2 - to the Mn2 II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.",
author = "Rose, {Hannah R.} and Ghosh, {Manas K.} and Maggiolo, {Ailiena O.} and Pollock, {Christopher J.} and Blaesi, {Elizabeth J.} and Viviane Hajj and Yifeng Wei and Rajakovich, {Lauren J.} and Chang, {Wei Chen} and Yilin Han and Mariana Hajj and Carsten Krebs and Alexey Silakov and Pandelia, {Maria Eirini} and {Bollinger, Jr.}, {Joseph M.} and Boal, {Amie Kathleen}",
year = "2018",
month = "5",
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doi = "10.1021/acs.biochem.8b00247",
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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, Jr., JM & Boal, AK 2018, 'Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class i Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor', Biochemistry, vol. 57, no. 18, pp. 2679-2693. https://doi.org/10.1021/acs.biochem.8b00247

Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class i Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor. / Rose, Hannah R.; Ghosh, Manas K.; Maggiolo, Ailiena O.; Pollock, Christopher J.; Blaesi, Elizabeth J.; Hajj, Viviane; Wei, Yifeng; Rajakovich, Lauren J.; Chang, Wei Chen; Han, Yilin; Hajj, Mariana; Krebs, Carsten; Silakov, Alexey; Pandelia, Maria Eirini; Bollinger, Jr., Joseph M.; Boal, Amie Kathleen.

In: Biochemistry, Vol. 57, No. 18, 08.05.2018, p. 2679-2693.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class i Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor

AU - Rose, Hannah R.

AU - Ghosh, Manas K.

AU - Maggiolo, Ailiena O.

AU - Pollock, Christopher J.

AU - Blaesi, Elizabeth J.

AU - Hajj, Viviane

AU - Wei, Yifeng

AU - Rajakovich, Lauren J.

AU - Chang, Wei Chen

AU - Han, Yilin

AU - Hajj, Mariana

AU - Krebs, Carsten

AU - Silakov, Alexey

AU - Pandelia, Maria Eirini

AU - Bollinger, Jr., Joseph M.

AU - Boal, Amie Kathleen

PY - 2018/5/8

Y1 - 2018/5/8

N2 - A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae (Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2 -) for activation, but it does not require the O2 --supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive "met" (III/III) forms seen with I(a-c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O2 - to the Mn2 II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.

AB - A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae (Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O2 -) for activation, but it does not require the O2 --supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins. Rather, Fj β directly deploys an oxidized dimanganese cofactor for radical initiation. In treatment with one-electron reductants, the cofactor can undergo cooperative three-electron reduction to the II/II state, in contrast to the quantitative univalent reduction to inactive "met" (III/III) forms seen with I(a-c) βs. This tendency makes Fj β unusually robust, as the II/II form can readily be reactivated. The structure of the protein rationalizes its distinctive traits. A distortion in a core helix of the ferritin-like architecture renders the active site unusually open, introduces a cavity near the cofactor, and positions a subclass-d-specific Lys residue to shepherd O2 - to the Mn2 II/II cluster. Relative to the positions of the radical tyrosines in the Ia/b proteins, the unreactive Tyr 104 of Fj β is held away from the cofactor by a hydrogen bond with a subclass-d-specific Thr residue. Structural comparisons, considered with its uniquely simple mode of activation, suggest that the Id protein might most closely resemble the primordial RNR-β.

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