The tyrosine free radical in ribonucleotide reductase from Escherichia coli.

Sjoberg, B.M.; Reichard, Peter; Gräslund, Astrid; Ehrenberg, Anders

doi:10.1016/s0021-9258(17)37999-1

Cited by 195 publications

(72 citation statements)

References 12 publications

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“…The discovery in 1972 of a stable Tyr122c radical in the b 2 subunit of the enzyme stimulated research to understand its role in catalysis. [53][54][55][56] Until recently no structure of the intact a 2 b 2 enzyme was available, although structures of both the a 2 and b 2 subunits had been determined. 57,58 A docking model of the holo-enzyme constructed from the two subunits suggested that the distance from Tyr122c in b 2 to the Cys439 in residue a 2 that initiates nucleotide reduction could be as long as 35Å.…”

Section: Ribonucleotide Reductasementioning

confidence: 99%

Functional and protective hole hopping in metalloenzymes

Gray

2021

Chem. Sci.

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Section: Ribonucleotide Reductasementioning

confidence: 99%

Functional and protective hole hopping in metalloenzymes

Gray

2021

Chem. Sci.

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“…35 The enzyme is inhibited by a range of iron chelators, not by direct interaction with the enzyme, but rather by depletion of the labile iron pool. 36,37 The active site contains two iron atoms coordinated by four carboxylates and two histidine ligands which are anti-ferromagnetically coupled by a μ-oxo bridge 38 (Fig. 2B).…”

Section: Cytosolic Iron(ii)-dependent Enzymesmentioning

confidence: 99%

Iron speciation in the cytosol: an overview

2013

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The nature of the cytosolic iron pool remains largely uncharacterized, although a range of candidate ligands and chaperones have been proposed. Herein an overview is presented of cytosolic non heme and non iron-sulphur cluster protein iron binding sites and the influence of ligands on the redox activity of iron. This analysis leads to the concept of iron(II) glutathione functioning as the labile cytosolic iron pool and offers a means for the selection of iron over manganese in subsequent incorporation into a wide range of iron-dependent enzymes and electron transfer proteins. Glutathione and glutathione-binding glutaredoxins play a critical role in iron sulfur cluster synthesis and Fe(II)GS (iron(II) coordinated by the thiol function of glutathione) is a suitable iron donor for this biosynthetic route. Significantly, both glutathione and glutaredoxins are universally distributed and thus a controlling influence of glutathione on intracellular iron trafficking is likely to be a common feature of the majority of living organisms.

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“…Due to its exceptional stability, this radical has served as a prototype for the characterization of tyrosyl radicals in various proteins and organisms. The EPR spectrum of Y • 122 exhibits a prominent doublet splitting arising from the sizeable hf interaction of one of the β-methylene protons (H β 1 ), which was already recognized over 50 years ago [17,18]. Isotopic labelling experiments have been used extensively in related EPR studies [18] and ENDOR experiments [11], which also allowed the identification of the hf coupling parameters of the ring protons.…”

Section: Introductionmentioning

confidence: 99%

“…The EPR spectrum of Y • 122 exhibits a prominent doublet splitting arising from the sizeable hf interaction of one of the β-methylene protons (H β 1 ), which was already recognized over 50 years ago [17,18]. Isotopic labelling experiments have been used extensively in related EPR studies [18] and ENDOR experiments [11], which also allowed the identification of the hf coupling parameters of the ring protons. Despite substantial efforts, no unambiguous determination of a smaller H β 2 hf interaction could be achieved.…”

Section: Introductionmentioning

confidence: 99%

Distribution of H$$^\upbeta$$ Hyperfine Couplings in a Tyrosyl Radical Revealed by 263 GHz ENDOR Spectroscopy

et al. 2021

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Abstract$$^1$$ 1 H ENDOR spectra of tyrosyl radicals (Y$$^\bullet$$ ∙ ) have been the subject of numerous EPR spectroscopic studies due to their importance in biology. Nevertheless, assignment of all internal $$^1$$ 1 H hyperfine couplings has been challenging because of substantial spectral overlap. Recently, using 263 GHz ENDOR in conjunction with statistical analysis, we could identify the signature of the H$$^{\upbeta _2}$$ β 2 coupling in the essential Y$$_{122}$$ 122 radical of Escherichia coli ribonucleotide reductase, and modeled it with a distribution of radical conformations. Here, we demonstrate that this analysis can be extended to the full-width $$^1$$ 1 H ENDOR spectra that contain the larger H$$^{\upbeta _1}$$ β 1 coupling. The H$$^{\upbeta _2}$$ β 2 and H$$^{\upbeta _1}$$ β 1 couplings are related to each other through the ring dihedral and report on the amino acid conformation. The 263 GHz ENDOR data, acquired in batches instead of averaging, and data processing by a new “drift model” allow reconstructing the ENDOR spectra with statistically meaningful confidence intervals and separating them from baseline distortions. Spectral simulations using a distribution of ring dihedral angles confirm the presence of a conformational distribution, consistent with the previous analysis of the H$$^{\upbeta _2}$$ β 2 coupling. The analysis was corroborated by 94 GHz $$^2$$ 2 H ENDOR of deuterated Y$$_{122}^\bullet$$ 122 ∙ . These studies provide a starting point to investigate low populated states of tyrosyl radicals in greater detail.

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The tyrosine free radical in ribonucleotide reductase from Escherichia coli.

Cited by 195 publications

References 12 publications

Functional and protective hole hopping in metalloenzymes

Functional and protective hole hopping in metalloenzymes

Iron speciation in the cytosol: an overview

Distribution of H$$^\upbeta$$ Hyperfine Couplings in a Tyrosyl Radical Revealed by 263 GHz ENDOR Spectroscopy

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