High-valent [MnFe] and [FeFe] cofactors in ribonucleotide reductases
(2012) In Biochimica et Biophysica Acta - Bioenergetics 1817(3). p.430-444- Abstract
Ribonucleotide reductases (RNRs) are essential for DNA synthesis in most organisms. In class-Ic RNR from Chlamydia trachomatis (Ct), a MnFe cofactor in subunit R2 forms the site required for enzyme activity, instead of an FeFe cofactor plus a redox-active tyrosine in class-Ia RNRs, for example in mouse (Mus musculus, Mm). For R2 proteins from Ct and Mm, either grown in the presence of, or reconstituted with Mn and Fe ions, structural and electronic properties of higher valence MnFe and FeFe sites were determined by X-ray absorption spectroscopy and complementary techniques, in combination with bond-valence-sum and density functional theory calculations. At least ten different cofactor species could be tentatively distinguished. In Ct... (More)
Ribonucleotide reductases (RNRs) are essential for DNA synthesis in most organisms. In class-Ic RNR from Chlamydia trachomatis (Ct), a MnFe cofactor in subunit R2 forms the site required for enzyme activity, instead of an FeFe cofactor plus a redox-active tyrosine in class-Ia RNRs, for example in mouse (Mus musculus, Mm). For R2 proteins from Ct and Mm, either grown in the presence of, or reconstituted with Mn and Fe ions, structural and electronic properties of higher valence MnFe and FeFe sites were determined by X-ray absorption spectroscopy and complementary techniques, in combination with bond-valence-sum and density functional theory calculations. At least ten different cofactor species could be tentatively distinguished. In Ct R2, two different Mn(IV)Fe(III) site configurations were assigned either L 4Mn IV(μO) 2Fe IIIL 4 (metal-metal distance of ∼ 2.75 Å, L = ligand) prevailing in metal-grown R2, or L 4Mn IV(μO)(μOH)Fe IIIL 4 (∼ 2.90 Å) dominating in metal-reconstituted R2. Specific spectroscopic features were attributed to an Fe(IV)Fe(III) site (∼ 2.55 Å) with a L 4Fe IV(μO) 2Fe IIIL 3 core structure. Several Mn,Fe(III)Fe(III) (∼ 2.9-3.1 Å) and Mn,Fe(III)Fe(II) species (∼ 3.3-3.4 Å) likely showed 5-coordinated Mn(III) or Fe(III). Rapid X-ray photoreduction of iron and shorter metal-metal distances in the high-valent states suggested radiation-induced modifications in most crystal structures of R2. The actual configuration of the MnFe and FeFe cofactors seems to depend on assembly sequences, bound metal type, valence state, and previous catalytic activity involving subunit R1. In Ct R2, the protonation of a bridging oxide in the Mn IV(μO)(μOH)Fe III core may be important for preventing premature site reduction and initiation of the radical chemistry in R1.
(Less)
- author
- Leidel, Nils ; Popović-Bijelić, Ana ; Havelius, Kajsa G.V. LU ; Chernev, Petko ; Voevodskaya, Nina ; Gräslund, Astrid and Haumann, Michael
- publishing date
- 2012-03-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Chlamydia, MnFe cofactor, Redox intermediate, Ribonucleotide reductase, X-ray absorption spectroscopy
- in
- Biochimica et Biophysica Acta - Bioenergetics
- volume
- 1817
- issue
- 3
- pages
- 15 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:84855870391
- pmid:22222354
- ISSN
- 0005-2728
- DOI
- 10.1016/j.bbabio.2011.12.008
- language
- English
- LU publication?
- no
- id
- babc1a39-3570-4fa4-b50b-35355d9a1fb6
- date added to LUP
- 2020-01-15 10:21:30
- date last changed
- 2024-01-02 03:48:58
@article{babc1a39-3570-4fa4-b50b-35355d9a1fb6,
abstract = {{<p>Ribonucleotide reductases (RNRs) are essential for DNA synthesis in most organisms. In class-Ic RNR from Chlamydia trachomatis (Ct), a MnFe cofactor in subunit R2 forms the site required for enzyme activity, instead of an FeFe cofactor plus a redox-active tyrosine in class-Ia RNRs, for example in mouse (Mus musculus, Mm). For R2 proteins from Ct and Mm, either grown in the presence of, or reconstituted with Mn and Fe ions, structural and electronic properties of higher valence MnFe and FeFe sites were determined by X-ray absorption spectroscopy and complementary techniques, in combination with bond-valence-sum and density functional theory calculations. At least ten different cofactor species could be tentatively distinguished. In Ct R2, two different Mn(IV)Fe(III) site configurations were assigned either L <sub>4</sub>Mn <sup>IV</sup>(μO) <sub>2</sub>Fe <sup>III</sup>L <sub>4</sub> (metal-metal distance of ∼ 2.75 Å, L = ligand) prevailing in metal-grown R2, or L <sub>4</sub>Mn <sup>IV</sup>(μO)(μOH)Fe <sup>III</sup>L <sub>4</sub> (∼ 2.90 Å) dominating in metal-reconstituted R2. Specific spectroscopic features were attributed to an Fe(IV)Fe(III) site (∼ 2.55 Å) with a L <sub>4</sub>Fe <sup>IV</sup>(μO) <sub>2</sub>Fe <sup>III</sup>L <sub>3</sub> core structure. Several Mn,Fe(III)Fe(III) (∼ 2.9-3.1 Å) and Mn,Fe(III)Fe(II) species (∼ 3.3-3.4 Å) likely showed 5-coordinated Mn(III) or Fe(III). Rapid X-ray photoreduction of iron and shorter metal-metal distances in the high-valent states suggested radiation-induced modifications in most crystal structures of R2. The actual configuration of the MnFe and FeFe cofactors seems to depend on assembly sequences, bound metal type, valence state, and previous catalytic activity involving subunit R1. In Ct R2, the protonation of a bridging oxide in the Mn <sup>IV</sup>(μO)(μOH)Fe <sup>III</sup> core may be important for preventing premature site reduction and initiation of the radical chemistry in R1.</p>}},
author = {{Leidel, Nils and Popović-Bijelić, Ana and Havelius, Kajsa G.V. and Chernev, Petko and Voevodskaya, Nina and Gräslund, Astrid and Haumann, Michael}},
issn = {{0005-2728}},
keywords = {{Chlamydia; MnFe cofactor; Redox intermediate; Ribonucleotide reductase; X-ray absorption spectroscopy}},
language = {{eng}},
month = {{03}},
number = {{3}},
pages = {{430--444}},
publisher = {{Elsevier}},
series = {{Biochimica et Biophysica Acta - Bioenergetics}},
title = {{High-valent [MnFe] and [FeFe] cofactors in ribonucleotide reductases}},
url = {{http://dx.doi.org/10.1016/j.bbabio.2011.12.008}},
doi = {{10.1016/j.bbabio.2011.12.008}},
volume = {{1817}},
year = {{2012}},
}