The manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase: structure, assembly, radical initiation, and evolution

J. Martin Bollinger, Wei Jiang, Michael T. Green, Carsten Krebs

Research output: Contribution to journalReview article

48 Citations (Scopus)

Abstract

The catalytic mechanism of a class I ribonucleotide reductase (RNR) is initiated by the generation of a hydrogen-abstracting thiyl radical via a conformationally gated, proton-coupled electron-transfer (PCET) from a cysteine residue in the α2 subunit over ∼35 Å to the cofactor in the β2 subunit. A chain of aromatic amino acids that spans the two subunits mediates this long-distance PCET by the formation of transient side-chain radicals. Details of the conformational gating, proton coupling, and 'radical-hopping' have, until very recently, been largely obscured by the failure of intermediate states to accumulate to high levels and the absence of sufficiently sensitive spectroscopic handles for intermediates that may accumulate to trace levels. In the most recently recognized subclass (c) of class I, founded by the enzyme from Chlamydia trachomatis (Ct), the stable tyrosyl radical that serves as the PCET acceptor in the conventional (subclass a or b) class I RNRs is functionally replaced by the MnIV ion of a MnIV/FeIII cofactor, which assembles in Ct β2 in place of the Fe2III/III cluster of the conventional β2s. The discovery of this novel radical-initiation cofactor and mechanism has raised intriguing questions concerning the evolution of class I RNRs and affords new opportunities for understanding the gated PCET step that initiates their catalytic mechanism.

Original languageEnglish (US)
Pages (from-to)650-657
Number of pages8
JournalCurrent Opinion in Structural Biology
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2008

Fingerprint

Ribonucleotide Reductases
Chlamydia trachomatis
Manganese
Protons
Iron
Electrons
Aromatic Amino Acids
Cysteine
Hydrogen
Ions
Enzymes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

@article{685b68da0bd44a53a9b81df84b0dd723,
title = "The manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase: structure, assembly, radical initiation, and evolution",
abstract = "The catalytic mechanism of a class I ribonucleotide reductase (RNR) is initiated by the generation of a hydrogen-abstracting thiyl radical via a conformationally gated, proton-coupled electron-transfer (PCET) from a cysteine residue in the α2 subunit over ∼35 {\AA} to the cofactor in the β2 subunit. A chain of aromatic amino acids that spans the two subunits mediates this long-distance PCET by the formation of transient side-chain radicals. Details of the conformational gating, proton coupling, and 'radical-hopping' have, until very recently, been largely obscured by the failure of intermediate states to accumulate to high levels and the absence of sufficiently sensitive spectroscopic handles for intermediates that may accumulate to trace levels. In the most recently recognized subclass (c) of class I, founded by the enzyme from Chlamydia trachomatis (Ct), the stable tyrosyl radical that serves as the PCET acceptor in the conventional (subclass a or b) class I RNRs is functionally replaced by the MnIV ion of a MnIV/FeIII cofactor, which assembles in Ct β2 in place of the Fe2III/III cluster of the conventional β2s. The discovery of this novel radical-initiation cofactor and mechanism has raised intriguing questions concerning the evolution of class I RNRs and affords new opportunities for understanding the gated PCET step that initiates their catalytic mechanism.",
author = "Bollinger, {J. Martin} and Wei Jiang and Green, {Michael T.} and Carsten Krebs",
year = "2008",
month = "12",
day = "1",
doi = "10.1016/j.sbi.2008.11.007",
language = "English (US)",
volume = "18",
pages = "650--657",
journal = "Current Opinion in Structural Biology",
issn = "0959-440X",
publisher = "Elsevier Limited",
number = "6",

}

TY - JOUR

T1 - The manganese(IV)/iron(III) cofactor of Chlamydia trachomatis ribonucleotide reductase

T2 - structure, assembly, radical initiation, and evolution

AU - Bollinger, J. Martin

AU - Jiang, Wei

AU - Green, Michael T.

AU - Krebs, Carsten

PY - 2008/12/1

Y1 - 2008/12/1

N2 - The catalytic mechanism of a class I ribonucleotide reductase (RNR) is initiated by the generation of a hydrogen-abstracting thiyl radical via a conformationally gated, proton-coupled electron-transfer (PCET) from a cysteine residue in the α2 subunit over ∼35 Å to the cofactor in the β2 subunit. A chain of aromatic amino acids that spans the two subunits mediates this long-distance PCET by the formation of transient side-chain radicals. Details of the conformational gating, proton coupling, and 'radical-hopping' have, until very recently, been largely obscured by the failure of intermediate states to accumulate to high levels and the absence of sufficiently sensitive spectroscopic handles for intermediates that may accumulate to trace levels. In the most recently recognized subclass (c) of class I, founded by the enzyme from Chlamydia trachomatis (Ct), the stable tyrosyl radical that serves as the PCET acceptor in the conventional (subclass a or b) class I RNRs is functionally replaced by the MnIV ion of a MnIV/FeIII cofactor, which assembles in Ct β2 in place of the Fe2III/III cluster of the conventional β2s. The discovery of this novel radical-initiation cofactor and mechanism has raised intriguing questions concerning the evolution of class I RNRs and affords new opportunities for understanding the gated PCET step that initiates their catalytic mechanism.

AB - The catalytic mechanism of a class I ribonucleotide reductase (RNR) is initiated by the generation of a hydrogen-abstracting thiyl radical via a conformationally gated, proton-coupled electron-transfer (PCET) from a cysteine residue in the α2 subunit over ∼35 Å to the cofactor in the β2 subunit. A chain of aromatic amino acids that spans the two subunits mediates this long-distance PCET by the formation of transient side-chain radicals. Details of the conformational gating, proton coupling, and 'radical-hopping' have, until very recently, been largely obscured by the failure of intermediate states to accumulate to high levels and the absence of sufficiently sensitive spectroscopic handles for intermediates that may accumulate to trace levels. In the most recently recognized subclass (c) of class I, founded by the enzyme from Chlamydia trachomatis (Ct), the stable tyrosyl radical that serves as the PCET acceptor in the conventional (subclass a or b) class I RNRs is functionally replaced by the MnIV ion of a MnIV/FeIII cofactor, which assembles in Ct β2 in place of the Fe2III/III cluster of the conventional β2s. The discovery of this novel radical-initiation cofactor and mechanism has raised intriguing questions concerning the evolution of class I RNRs and affords new opportunities for understanding the gated PCET step that initiates their catalytic mechanism.

UR - http://www.scopus.com/inward/record.url?scp=57049085691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57049085691&partnerID=8YFLogxK

U2 - 10.1016/j.sbi.2008.11.007

DO - 10.1016/j.sbi.2008.11.007

M3 - Review article

C2 - 19046875

AN - SCOPUS:57049085691

VL - 18

SP - 650

EP - 657

JO - Current Opinion in Structural Biology

JF - Current Opinion in Structural Biology

SN - 0959-440X

IS - 6

ER -