Structural analysis of the Mn(IV)/Fe(III) cofactor of Chlamydia trachomatis ribonucleotide reductase by extended X-ray absorption fine structure spectroscopy and density functional theory calculations

Jarod M. Younker, Courtney M. Krest, Wei Jiang, Carsten Krebs, Joseph M. Bollinger, Jr., Michael T. Green

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Abstract

The class Ic ribonucleotide reductase from Chlamydia trachomatis (Ct) uses a stable Mn(IV)/Fe(III) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of ∼2.92 Å. The Mn data also suggest the presence of a short 1.74 Å Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe 2 (III/III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH x ligands as well as the location of the Mn(IV) ion (site 1 or 2). The models that agree best with experimental observation feature a μ-1,3-carboxylate bridge (E120), terminal solvent (H 2 O/OH) to site 1, one μ-O bridge, and one μ-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.

Original languageEnglish (US)
Pages (from-to)15022-15027
Number of pages6
JournalJournal of the American Chemical Society
Volume130
Issue number45
DOIs
StatePublished - Nov 12 2008

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Extended X ray absorption fine structure spectroscopy
Ribonucleotide Reductases
Chlamydia trachomatis
Structural analysis
Density functional theory
Spectrum Analysis
X-Rays
Ions
Free Radicals
Nucleotides
Metals
Protonation
Observation
X ray absorption
Ligands
Free radicals
Intermetallics
Metal ions
Crystal structure
Proteins

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

@article{c61cca86b5dd44eb9544c4d1a0a8ba3c,
title = "Structural analysis of the Mn(IV)/Fe(III) cofactor of Chlamydia trachomatis ribonucleotide reductase by extended X-ray absorption fine structure spectroscopy and density functional theory calculations",
abstract = "The class Ic ribonucleotide reductase from Chlamydia trachomatis (Ct) uses a stable Mn(IV)/Fe(III) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of ∼2.92 {\AA}. The Mn data also suggest the presence of a short 1.74 {\AA} Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe 2 (III/III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH x ligands as well as the location of the Mn(IV) ion (site 1 or 2). The models that agree best with experimental observation feature a μ-1,3-carboxylate bridge (E120), terminal solvent (H 2 O/OH) to site 1, one μ-O bridge, and one μ-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.",
author = "Younker, {Jarod M.} and Krest, {Courtney M.} and Wei Jiang and Carsten Krebs and {Bollinger, Jr.}, {Joseph M.} and Green, {Michael T.}",
year = "2008",
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T1 - Structural analysis of the Mn(IV)/Fe(III) cofactor of Chlamydia trachomatis ribonucleotide reductase by extended X-ray absorption fine structure spectroscopy and density functional theory calculations

AU - Younker, Jarod M.

AU - Krest, Courtney M.

AU - Jiang, Wei

AU - Krebs, Carsten

AU - Bollinger, Jr., Joseph M.

AU - Green, Michael T.

PY - 2008/11/12

Y1 - 2008/11/12

N2 - The class Ic ribonucleotide reductase from Chlamydia trachomatis (Ct) uses a stable Mn(IV)/Fe(III) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of ∼2.92 Å. The Mn data also suggest the presence of a short 1.74 Å Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe 2 (III/III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH x ligands as well as the location of the Mn(IV) ion (site 1 or 2). The models that agree best with experimental observation feature a μ-1,3-carboxylate bridge (E120), terminal solvent (H 2 O/OH) to site 1, one μ-O bridge, and one μ-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.

AB - The class Ic ribonucleotide reductase from Chlamydia trachomatis (Ct) uses a stable Mn(IV)/Fe(III) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of ∼2.92 Å. The Mn data also suggest the presence of a short 1.74 Å Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe 2 (III/III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH x ligands as well as the location of the Mn(IV) ion (site 1 or 2). The models that agree best with experimental observation feature a μ-1,3-carboxylate bridge (E120), terminal solvent (H 2 O/OH) to site 1, one μ-O bridge, and one μ-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.

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