Glyceraldehyde‐3‐phosphate dehydrogenase from <i>Citrobacter</i> sp. S‐77 is post‐translationally modified by CoA (protein CoAlation) under oxidative stress

Tsuji, Kohei; Yoon, Ki Seok; Ogo, Seiji

doi:10.1002/2211-5463.12542

Cited by 14 publications

(17 citation statements)

References 65 publications

(168 reference statements)

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“…In addition to intra/intermolecular disulfide bond formation, GAPDH can also form mixed disulfide bonds with LMW thiols, which serve as cellular redox buffers and contribute to the protection of proteins from H 2 O 2 and other oxidants [ 60 , 61 ]. GAPDH has been reported to form mixed-disulfides with various LMW thiols, including glutathione (GSH—eukaryotes and Gram-negative bacteria), bacillithiol (BSH—Gram-positive Firmicutes), mycothiol (MSH—Actinobacteria) and coenzyme A (CoA—all organisms) ( Figure 2 , Table 2 ) [ 20 , 40 , 46 , 47 , 58 , 59 , 62 ].…”

Section: Gapdh Modifications By Redox Writersmentioning

confidence: 99%

The Writers, Readers, and Erasers in Redox Regulation of GAPDH

2020

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Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

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Section: Gapdh Modifications By Redox Writersmentioning

confidence: 99%

The Writers, Readers, and Erasers in Redox Regulation of GAPDH

2020

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“…In addition to intra/intermolecular disulfide bond formation, GAPDH can also form mixed disulfide bonds with LMW thiols, which serve as cellular redox buffers and contribute to the protection of proteins from H2O2 and other oxidants [60,61]. GAPDH has been reported to form mixed disulfides with various LMW thiols, including glutathione (GSH -eukaryotes and Gramnegative bacteria), bacillithiol (BSH -Gram-positive Firmicutes), mycothiol (MSH -Actinobacteria) and coenzyme A (CoA -all organisms) ( Figure 2 and Table 2) [20,40,46,47,58,59,62].…”

Section: Sulfenylation and S-thiolation Of Gapdhmentioning

confidence: 99%

“…in mammalian cells and tissues, and in bacteria (Gram-positive S. aureus and B. subtilis, and Gram-negative Citobacter sp. 5-77) [20,44,62]. Tsuchiya et al (2018) reported the reversible inactivation of Sa-GAPDH upon CoAlation [20].…”

Section: Sulfenylation and S-thiolation Of Gapdhmentioning

confidence: 99%

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The Writers, Readers and Erasers in Redox Regulation of GAPDH

Tossounian¹,

Zhang²,

Gout³

2020

Preprint

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Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH towards different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g. sulfenylation, S-thiolation, nitrosylation and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

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“…the formation of mixed disulfide bonds between small thiol‐containing compounds and protein cysteinyl thiol groups. Within the field of oxidative stress, mass spectrometry has been used to detect protein thiol oxidations such as to sulfenic acid, 20–23 sulfinic acid, 24 sulfonic acid, 25–27 S‐thiolation by coenzyme A, 28 hydrogen sulfide, 29 cysteine perthiosulfenic acid, 30 S‐nitrosylation, 31–34 cysteine 35,36 and glutathionylation, 37–40 and to a lesser extent protein S‐thiolation by HcySH 41,42 …”

Section: Introductionmentioning

confidence: 99%

Investigating protein thiol chemistry associated with dehydroascorbate, homocysteine and glutathione using mass spectrometry

Ahuie

Gagnon

Pace

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale:Oxidative stress is an imbalance between reactive free radical oxygen species and antioxidant defenses. Its consequences can lead to numerous pathologies. Regulating oxidative stress is the complex interplay between antioxidant recycling and thiol-containing regulatory proteins. Understanding these regulatory mechanisms is important for preventing onset of oxidative stress. The aim of this study was to investigate S-thiol protein chemistry associated with oxidized vitamin C (dehydroascorbate, DHA), homocysteine (HcySH) and glutathione (GSH) using mass spectrometry. Methods:Glutaredoxin-1 (Grx-1) was incubated with DHA, with and without GSH and HcySH. Disulfide formation was followed by electrospray ionization mass spectrometry (ESI-MS) of intact proteins and by LC/ESI-MS/MS of peptides from protein tryptic digestions. The mechanism of DHA-mediated S-thiolation was investigated using two synthetic peptides: AcFHACAAK and AcFHACE. Three proteins, i.e. human hemoglobin (HHb), recombinant peroxiredoxin 2 (Prdx2) andGrx-1, were S-homocysteinylated followed by S-transthiolyation with GSH and investigated by ESI-MS and ESI-MS/MS. Results: ESI-MS analysis reveals that DHA mediates disulfide formation andS-thiolation by HcySH as well as GSH of Grx-1. LC/ESI-MS/MS analysis allows identification of Grx-1 S-thiolated cysteine adducts. The mechanism by which DHA mediates S-thiolation of heptapeptide AcFHACAAK is shown to be via initial formation of a thiohemiketal adduct. In addition, ESI-MS of intact proteins shows that GSH can S-transthiolate S-homocysteinylated Grx-1, HHb and Prdx2.The GS-S-protein adducts over time dominate the ESI-MS spectrum profile. Conclusions:Mass spectrometry is a unique analytical technique for probing complex reaction mechanisms associated with oxidative stress. Using model proteins, ESI-MS reveals the mechanism of DHA-facilitated S-thiolation, which consists of thiohemiketal formation, disulfide formation or S-thiolation. Furthermore, protein S-thiolation by HcySH can be reversed by reversible GSH thiol exchange. The use of mass spectrometry with in vitro models of protein S-thiolation in oxidative stress may provide significant insight into possible mechanisms of action occurring in vivo.

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Glyceraldehyde‐3‐phosphate dehydrogenase from Citrobacter sp. S‐77 is post‐translationally modified by CoA (protein CoAlation) under oxidative stress

Cited by 14 publications

References 65 publications

The Writers, Readers, and Erasers in Redox Regulation of GAPDH

The Writers, Readers, and Erasers in Redox Regulation of GAPDH

The Writers, Readers and Erasers in Redox Regulation of GAPDH

Investigating protein thiol chemistry associated with dehydroascorbate, homocysteine and glutathione using mass spectrometry

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