Reactivity of Thioredoxin as a Protein Thiol-Disulfide Oxidoreductase

Cheng, Zhiyong; Zhang, Jinfeng; Ballou, David P.; Williams, Charles H.

doi:10.1021/cr100006x

Cited by 117 publications

(94 citation statements)

References 145 publications

(645 reference statements)

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“…Mass spectrometry data reveal a second intramolecular disulfide besides the active site disulfide, formed between Cys-62 and Cys-69 under oxidizing conditions (14). The formation of the second disulfide between Cys-62 and Cys-69 impairs Trx1 activity and is predicted to have a profound effect by disrupting interactions between Trx and its target protein (6,14,15). In vitro, a two-disulfide form of Trx1 (Trx1-S 4 ) is inactive either as a disulfide reductase or as a substrate for TrxR and is no longer an anti-apoptotic factor via ASK1, supporting the interpretation that oxidation of the non-active site dithiol could possibly provide a structural switch affecting Trx1 function during oxidative stress and redox signaling (14,16).…”

mentioning

confidence: 99%

Thioredoxin 1 Is Inactivated Due to Oxidation Induced by Peroxiredoxin under Oxidative Stress and Reactivated by the Glutaredoxin System

Du¹,

Zhang²,

Zhang

et al. 2013

Journal of Biological Chemistry

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Background:The Cys-62/Cys-69 dithiol of Trx1 is predicted to have a profound effect on cell signaling. Results: The Cys-62/Cys-69 dithiol of Trx1 was oxidized by Prx1, and this disulfide was reduced by the GSH/glutaredoxin system. Conclusion: Trx1 is involved in redox regulation via reversible oxidation of the Cys-62/Cys-69 dithiol of Trx1. Significance: We demonstrated the critical role of Trx1 oxidation in cell signaling.

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confidence: 99%

Thioredoxin 1 Is Inactivated Due to Oxidation Induced by Peroxiredoxin under Oxidative Stress and Reactivated by the Glutaredoxin System

Du¹,

Zhang²,

Zhang

et al. 2013

Journal of Biological Chemistry

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“…In ''classical'' Trx, P76 and G92 occupy the central positions in two loops, that together with the active site cysteine motif, form the substrate binding site (the so-called substrate recognition loop motif), which is structurally conserved among Trx-fold proteins [10]. D26 is indispensable for the function of ''classical'' Trx, but its detailed role in the catalytic mechanism is not firmly established [31,52]. Several lines of experimental evidence support the role of D26 as a base facilitating deprotonation of C c that attacks the intermolecular disulfide bond between Trx and the target protein during the catalytic cycle [30,31].…”

Section: Discussionmentioning

confidence: 99%

Lactococcus lactis TrxD represents a subgroup of thioredoxins prevalent in Gram-positive bacteria containing WCXDC active site motifs

Björnberg

Efler

Ebong

et al. 2014

Archives of Biochemistry and Biophysics

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“…Due to a low reduction potential of thiols and their ease to be oxidized to sulfur species, disulfide chemistry is very rich, which can wreak havoc in tightly spaced cellular compartments if not properly controlled 7,34,35,37,39 .…”

Section: Discussionmentioning

confidence: 99%

Single-molecule studies of disulfide bond reduction pathways used by human thioredoxin

Szoszkiewicz

2013

Biophysical Chemistry

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How to cite this manuscriptIf you make reference to this version of the manuscript, use the following information: Szoszkiewicz, R. (2013). Single-molecule studies of disulfide bond reduction pathways used by human thioredoxin. Retrieved from http://krex.ksu.edu Published Version InformationCitation: Szoszkiewicz, R. (2013 8 molecules are stretched at constant force applied by a cantilever in a force-clamp mode of atomic force microscopy (FC-AFM). Disulfide reduction events are accurately detected from stepwise increases in the end-to-end length of (I27 SS ) 8 . Earlier FC-AFM studies observed one disulfide reduction pathway used by hTrx and suggested an additional electron tunnelling mechanism. Here, a very large set of unbiased FC-AFM data is collected in a range of clamping forces. By analyzing the data using exponential fits and dwell times histograms two disulfide reduction pathways used by hTrx are resolved. Based on previous studies one of these pathways is attributed to force-dependent Michaelis-Menten catalysis. The latter reduction pathway is weakly forceinhibited and occurs sporadically. Bimolecular nucleophilic substitutions (S N 2) and electron tunnelling (ET) mechanisms are discussed to explain the second pathway. Direct S N 2 and ET mechanisms cannot be discounted, but a hypothetical E2-S N 2 mechanism involving a hydride reducing a disulfide bond provides an interesting alternative, which needs to be verified in future experiments.

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Reactivity of Thioredoxin as a Protein Thiol-Disulfide Oxidoreductase

Cited by 117 publications

References 145 publications

Thioredoxin 1 Is Inactivated Due to Oxidation Induced by Peroxiredoxin under Oxidative Stress and Reactivated by the Glutaredoxin System

Thioredoxin 1 Is Inactivated Due to Oxidation Induced by Peroxiredoxin under Oxidative Stress and Reactivated by the Glutaredoxin System

Lactococcus lactis TrxD represents a subgroup of thioredoxins prevalent in Gram-positive bacteria containing WCXDC active site motifs

Single-molecule studies of disulfide bond reduction pathways used by human thioredoxin

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