Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Paulsen, Candice E.; Carroll, Kate S.

doi:10.1021/cr300163e

Cited by 1,009 publications

(969 citation statements)

References 674 publications

(899 reference statements)

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“…No reducing activity of TCEP, GSH and DTT toward stable oxidative modifications of SH groups (sulfinic, sulfone, or sulfonate) was reported to our knowledge (46,47). However, TCEP was found to reduce sulfenic acids, the precursor to disulfides, S-nitroso groups (48,49), as well as S-sulfo peptides (50). Several reasons however suggest that these are highly unlikely to be significant contributors to the species assayed by the ICAT procedure used in this study.…”

Section: In Vitro Modeling Of Crystallin Cysteine Residue Oxidation Wmentioning

confidence: 74%

“…First, protein nitrosylation in lens, while studied in vitro (51), has not been reported in vivo. Second, although sulfenic acid is an important biological modification in cell signaling, the consensus is that it would be labile to the acidic conditions created by the TCA that we used for the ICAT procedure (49,52,53). Finally, the S-sulfo modification is an important by-product during in vitro peptide synthesis or protein oxidation via mixing with inorganic sulfate (50,54), but to our knowledge, it has not been described in biological proteins.…”

Section: In Vitro Modeling Of Crystallin Cysteine Residue Oxidation Wmentioning

confidence: 99%

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Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Fan¹,

Zhou

Wang

et al. 2015

Molecular & Cellular Proteomics

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Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathionedepleted LEGSKO mouse lenses for intra-versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was 4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H 2 O 2 , whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of age- Aging lens crystallins accumulate post-synthetic modifications that can be broadly classified into three categories, namely (1) protein backbone changes, such as racemization and truncation (1-3), (2) conversion of one amino acid into another, such as deamidation of asparagine into aspartate or deguanidination of arginine into ornithine, deamination of lysine into allysine and 2-aminoadipic acid (4 -6), and (3) amino acid residue damage from reactive carbonyls and reactive oxygen species (7,8). Carbonyl damage results from the Maillard Reaction by glucose, methylglyoxal, or oxidation products of ascorbate, tryptophan or lipids which form adducts and crosslinks with nucleophilic group of lysine, arginine and cysteine. Examples include carboxymethyl-lysine, pentosidine, methylglyoxal hydroimidazolones, HNE-cysteine adducts and kynurenine (7,9 -12). Oxidative damage results from reactive oxygen species that directly damage amino acid residues, e.g. oxidizing tryptophan into N-formyl kynurenine and kynurenine, methionine into its sulfoxide, and cysteine into cysteine disulfides or cysteic acid (13)(14)(15).Because of their relevance to age-related cataract, the impact of each of these modifications on crystallin structure and stability is the subject of intense investigation. Importantly, Benedek proposed that high molecular weight (HMW) 1 crystallin aggregates the size of 50 million daltons are needed in order for lens opacification to be visible (16,17). Crystallin aggregation conceivably occurs by o...

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Section: In Vitro Modeling Of Crystallin Cysteine Residue Oxidation Wmentioning

confidence: 74%

Section: In Vitro Modeling Of Crystallin Cysteine Residue Oxidation Wmentioning

confidence: 99%

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Fan¹,

Zhou

Wang

et al. 2015

Molecular & Cellular Proteomics

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“…[8][9][10][11][12][13] Biological thiols like glutathione and cysteine have multiple functions in vital biological processes in humans, animals and plants. [14][15][16][17] One key indicator of thiol reactivity is its pKa value. Generally, there are several methods available for pKa determination.…”

Section: Introduction To Thiolsmentioning

confidence: 99%

Evaluation of Thiol Raman Activities and pK_a Values Using Internally Referenced Raman-Based pH Titration

Suwandaratne

Siriwardana

et al. 2016

Anal. Chem.

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“…The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications, including S-sulfenylation (-SOH), S-sulfinylation (-SO 2 H), S-sulfonylation (-SO 3 H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), and S-glutathionylation (-SSG) ( Fig. 1) (3,4). Most thiol redox modifications can be formed by the non-enzymatic reactions of reactive oxygen/nitrogen/sulfur species (ROS/RNS/RSS) with protein thiols, which has led to the widespread notion that these types of modifications are randomly distributed across the cysteine proteome.…”

mentioning

confidence: 99%

The Expanding Landscape of the Thiol Redox Proteome

Yang

Carroll

Liebler

2016

Molecular & Cellular Proteomics

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179

111

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Cysteine occupies a unique place in protein chemistry. The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications beyond classical thiol-disulfide redox equilibria, including S-sulfenylation (-SOH), S-sulfinylation (-SO 2 H), S-sulfonylation (-SO 3 H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), S-glutathionylation (-SSG), and others. Emerging evidence suggests that these post-translational modifications (PTM) are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding their roles in biology and disease. However, analysis of these highly labile and dynamic modifications poses challenges. Recent advances in the design of probes for thiol redox forms, together with innovative mass spectrometry based chemoproteomics methods make it possible to perform global, site-specific, and quantitative analyses of thiol redox modifications in complex proteomes.

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Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Cited by 1,009 publications

References 674 publications

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Evaluation of Thiol Raman Activities and pK_a Values Using Internally Referenced Raman-Based pH Titration

The Expanding Landscape of the Thiol Redox Proteome

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Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Cited by 1,009 publications

References 674 publications

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens*

Evaluation of Thiol Raman Activities and pKa Values Using Internally Referenced Raman-Based pH Titration

The Expanding Landscape of the Thiol Redox Proteome

Contact Info

Product

Resources

About

Evaluation of Thiol Raman Activities and pK_a Values Using Internally Referenced Raman-Based pH Titration