Intermolecular electron transfer in two-iron superoxide reductase: a putative role for the desulforedoxin center as an electron donor to the iron active site

Bonnot, F.; Duval, Simon; Lombard, Murielle; Valton, Julien; Houée-Levin⊥, Chantal; Nivière, Vincent

doi:10.1007/s00775-011-0788-5

Cited by 8 publications

(15 citation statements)

References 33 publications

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“…Thus, the equilibrium structure may be evolutionary optimized for intramolecular electron transfer, which provides an indirect indication for the biological relevance of this mechanism. Consistently, a quasi conserved tyrosine, previously proposed as an electron relay between the two metal sites, 46,47 represents an integral constituent of the identified intramolecular route.…”

Section: Discussionsupporting

confidence: 64%

“…Electron transfer pathways corresponding to the two subunits are colour-coded, and Fe atoms of centres I and II, depicted as green spheres, are labelled Fe1 and Fe2, respectively. The quasi conserved tyrosine between both metals sites, 43,46,47 Y115 in Dd 2Fe-SOR, is shown in green. C1 and C2 are two points on the C 2 crystallographic axis (not shown).…”

Section: Resultsmentioning

confidence: 99%

“…2 In principle, the rate of electron transfer decreases exponentially with the donor-acceptor distance; [57][58][59][60] however, examples of efficient biological electron transfer over similar distances have been reported. 58,[60][61][62] In this respect, a quasi conserved tyrosine between the two metal sites (see S1, ESI †) 43,46,47 or cellular electron shuttles could serve as additional relay sites for electron/hole hopping in 2Fe-SOR ( Fig. 1, 2B, and C).…”

Section: Introductionmentioning

confidence: 99%

“…30,31,[49][50][51][52] (B) Intramolecular electron transfer between centres I and II, possibly mediated by a quasi conserved tyrosine residue between the two (Y115 in Dd 2Fe-SOR). 43,46,47 (C) Intermolecular electron transfer between centres I and II involving a cellular electron shuttle. (D) Intermolecular electron transfer between centres I and II of two different 2Fe-SOR molecules.…”

Section: Introductionmentioning

confidence: 99%

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Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Horch

Utesch

Hildebrandt

et al. 2016

Phys. Chem. Chem. Phys.

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Superoxide reductases are non-heme iron enzymes that represent valuable model systems for the reductive detoxification of reactive oxygen species. In the present study, we applied different theoretical methods to study the structural dynamics of a prototypical 2Fe-superoxide reductase and its influence on electron transfer towards the active site. Using normal mode and essential dynamics analyses, we could show that enzymes of this type are capable of well-defined, electrostatically triggered domain movements, which may allow conformational proofreading for cellular redox partners involved in intermolecular electron transfer. Moreover, these global modes of motion were found to enable access to molecular configurations with decreased tunnelling distances between the active site and the enzyme's second iron centre. Using all-atom classical molecular dynamics simulations and the tunnelling pathway model, however, we found that electron transfer between the two metal sites is not accelerated under these conditions. This unexpected finding suggests that the unperturbed enzymatic structure is optimized for intramolecular electron transfer, which provides an indirect indication of the biological relevance of such a mechanism. Consistently, efficient electron transfer was found to depend on a distinct route, which is accessible via the equilibrium geometry and characterized by a quasi conserved tyrosine that could enable multistep-tunnelling (hopping). Besides these explicit findings, the present study demonstrates the importance of considering both global and local protein dynamics, and a generalized approach for the functional analysis of these aspects is provided.

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Horch

Utesch

Hildebrandt

et al. 2016

Phys. Chem. Chem. Phys.

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“… 3 The 600-nm intermediate in some 1Fe- and 2Fe-SORs undergoes a biphasic decay, which has been attributed to k 3 < k 2 in Scheme I (4, 7, 37). …”

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confidence: 99%

Treponema denticola Superoxide Reductase: In Vivo Role, in Vitro Reactivities, and a Novel [Fe(Cys)₄] Site

et al. 2012

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In vitro and in vivo results are presented demonstrating that superoxide reductase (SOR) from the airsensitive oral spirochete, Treponema denticola (Td), is a principal enzymatic scavenger of superoxide in this organism. This SOR contains the characteristic non-heme [Fe(His) 4 Cys] active sites. No other metal-binding domain has been annotated for Td SOR. However, we found that Td SOR also accommodates a [Fe(Cys) 4 ] site whose spectroscopic and redox properties resemble those in so-called 2Fe-SORs. Spectroscopic comparisons of the wild type and engineered Cys → Ser variants indicate that three of the Cys ligands correspond to those in [Fe(Cys) 4 ] sites of "canonical" 2Fe-SORs, whereas the fourth Cys ligand residue has no counterpart in canonical 2Fe-SORs or in any other known [Fe(Cys) 4 ] protein. Structural modeling is consistent with iron ligation of the "noncanonical" Cys residue across subunit interfaces of the Td SOR homodimer. The Td SOR was isolated with only a small percentage of [Fe(Cys) 4 ] sites. However, quantitative formation of stable [Fe(Cys) 4 ] sites was readily achieved by exposing the as-isolated protein to an iron salt, a disulfide reducing agent and air. The disulfide/dithiol status and iron occupancy of the Td SOR [Fe(Cys) 4 ] sites could, thus, reflect intracellular redox status, particularly during periods of oxidative stress.

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Superoxide Reductase: Different Interaction Modes with its Two Redox Partners

et al. 2013

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Anaerobic organisms have molecular systems to detoxify reactive oxygen species when transiently exposed to oxygen. One of these systems is superoxide reductase, which reduces O2 (.-) to H2 O2 without production of molecular oxygen. In order to complete the reduction of superoxide anion, superoxide reductase requires an electron, delivered by its redox partners, which in Desulfovibrio gigas are rubredoxin and/or desulforedoxin. In this work, we characterized the interaction of Desulfovibrio gigas superoxide reductase with both electron donors by using steady-state kinetics, 2D NMR titrations, and backbone relaxation measurements. The rubredoxin surface involved in the electron transfer complex with superoxide reductase comprises the solvent-exposed hydrophobic residues in the vicinity of its metal center (Cys9, Gly10, Cys42, Gly43, and Ala44), and a Kd of 3 μM at 59 mM ionic strength was estimated by NMR. The ionic strength dependence of superoxide-mediated rubredoxin oxidation by superoxide reductase has a maximum kapp of (37 ± 12) min(-1) at 157 mM. Relative to the electron donor desulforedoxin, its complex with superoxide reductase was not detected by chemical shift perturbation, though this protein is able to transfer electrons to superoxide reductase with a maximum kapp of (31 ± 7) min(-1) at an ionic strength of 57 mM. Competition experiments using steady-state kinetics and NMR spectroscopy (backbone relaxation measurements and use of a paramagnetic relaxation enhancement probe) with Fe-desulforedoxin in the presence of (15) N-Zn-rubredoxin showed that these two electron donors compete for the same site on the enzyme surface, as shown in the model structure of the complex generated by using restrained molecular docking calculations. These combined strategies indicate that the two small electron donors bind in different manners, with the desulforedoxin complex being a short lived electron transfer complex or more dynamic, with many equivalent kinetically competent orientations.

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Intermolecular electron transfer in two-iron superoxide reductase: a putative role for the desulforedoxin center as an electron donor to the iron active site

Cited by 8 publications

References 33 publications

Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Treponema denticola Superoxide Reductase: In Vivo Role, in Vitro Reactivities, and a Novel [Fe(Cys)₄] Site

Superoxide Reductase: Different Interaction Modes with its Two Redox Partners

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Intermolecular electron transfer in two-iron superoxide reductase: a putative role for the desulforedoxin center as an electron donor to the iron active site

Cited by 8 publications

References 33 publications

Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Domain motions and electron transfer dynamics in 2Fe-superoxide reductase

Treponema denticola Superoxide Reductase: In Vivo Role, in Vitro Reactivities, and a Novel [Fe(Cys)4] Site

Superoxide Reductase: Different Interaction Modes with its Two Redox Partners

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Product

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Treponema denticola Superoxide Reductase: In Vivo Role, in Vitro Reactivities, and a Novel [Fe(Cys)₄] Site