Peroxyl radical- and photo-oxidation of glucose 6-phosphate dehydrogenase generates cross-links and functional changes via oxidation of tyrosine and tryptophan residues

Leinisch, Fabian; Mariotti, Michele; Rykær, Martin; López-Alarcón, Camilo; Hägglund, Per; Davies, Michael J.

doi:10.1016/j.freeradbiomed.2017.07.025

Cited by 65 publications

(61 citation statements)

References 84 publications

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“…() emphasised that the reduced maximum UV absorption peak of proteins is mainly ascribed to the oxidative modification of tyrosine and tryptophan residues on protein surfaces. Similar to tryptophan residues, tyrosine is susceptible to oxidation by ROO· (Leinisch et al ., ), and a hydrogen atom‐abstracted reaction occurs at the heteroatom substitute (Zhang et al ., ), thereby producing tyrosyl phenoxyl radical (Jongberg et al ., ). The coupling of two tyrosyl radicals can further generate dityrosine via a covalent bond and consequently enhance intra‐ or inter‐ molecular protein crosslinking (Zhang et al ., 2017b).…”

Section: Resultsmentioning

confidence: 99%

“…It is possible therefore that ROOÁ may transfer to the folded regions and directly attack those buried amino acids. Among the aromatic amino acids, tyrosine and tryptophan residues are prone to oxidation by ROOÁ (Leinisch et al, 2017). The oxidation of these buried residues can result in protein unfolding (Zhang et al, 2013).…”

Section: Changes In Surface Hydrophobicitymentioning

confidence: 99%

“…On the one hand, ROOÁ can abstract a hydrogen atom from the S-H group of cysteine to produce thiyl radicals (Davies, 2016), which can further react with other thiol/thiolate to facilitate disulfide cross-linking (Zhang et al, 2013). On the other hand, the oxidation of tyrosine and tryptophan can result in the generation of tyrosine-tyrosine and tyrosine-tryptophan cross-links (Leinisch et al, 2017).…”

Section: Spectroscopy Analysismentioning

confidence: 99%

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Effect of peroxyl radicals on the structure and gel properties of isolated rabbit meat myofibrillar proteins

Wang

Gan

et al. 2018

Int J of Food Sci Tech

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Summary We investigated the effect of peroxyl radicals (ROO·), which are products of lipid peroxidation, on the structure and gel properties of myofibrillar proteins (MPs) isolated from rabbit meat. 2,2′‐Azobis(2‐amidinopropane) dihydrochloride (AAPH) was heated to stably derive ROO·. As the AAPH concentration increased, the protein carbonyl compounds significantly accumulated (P < 0.05), and the total sulfhydryl content was significantly lost (P < 0.05). Circular dichroism spectra, UV absorption spectra, intrinsic fluorescence spectra and surface hydrophobicity revealed that ROO· caused protein unfolding and conformational changes in MPs. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) analysis indicated that moderate (0–3 mm) and relatively high (5 and 10 mm) AAPH concentrations could lead to protein crosslinking and protein aggregation, respectively. These changes in protein structure could influence the gelling properties of MPs. Low‐level protein oxidation could increase gel strength and water holding capacity, whereas high‐level protein oxidation could reduce gel properties.

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Section: Resultsmentioning

confidence: 99%

Section: Changes In Surface Hydrophobicitymentioning

confidence: 99%

Section: Spectroscopy Analysismentioning

confidence: 99%

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Effect of peroxyl radicals on the structure and gel properties of isolated rabbit meat myofibrillar proteins

Wang

Gan

et al. 2018

Int J of Food Sci Tech

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“…5, 2018 More recently, oxidation of the enzyme glucose 6-phosphate dehydrogenase initiated by peroxyl radicals, or by photo-sensitized Rose Bengal, has been comprehensively compared. 54 This study showed inactivation of the enzyme and the formation of various cross-links between Tyr-Tyr and Trp-Tyr residues, depending on the oxidizing system. The photo-sensitization of Rose Bengal produces 1 O 2 , which led to the formation of Tyr276-Tyr284, Tyr451-Tyr461 and Trp 203-Tyr207 cross-links.…”

mentioning

confidence: 86%

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

Paviani

Galdino

Prazeres

et al. 2017

J. Braz. Chem. Soc.

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Protein oxidation is an unavoidable consequence of aerobic metabolism. The oxidation of most proteins residues is non-repairable and may affect protein structure and function. In particular, protein cross-links arising from oxidative modifications are presumably toxic to cells because they may accumulate and induce protein aggregation. However, most of these irreversible protein cross-links remain partially characterized. Up to very recently, ditryptophan cross-links (Trp-Trp), in particular, have been largely disregarded in the literature. Here, we briefly review studies showing that Trp-Trp cross-links can be formed in proteins exposed to a variety of oxidants. The challenges to fully characterize Trp-Trp cross-links are discussed as well as their potential roles in protein dysfunction and aggregation.Keywords: ditryptophan, cross-links, protein oxidation, free radicals Protein OxidationFree radicals and other oxidants are formed in living organisms by oxidation-reduction processes, which occur continuously during metabolism and through interactions with the environment. Organisms evolved enzymatic antioxidant defenses and the capability to use antioxidants from the diet to control the levels of these species. 1,2 Nevertheless, under certain circumstances, the levels of radicals and oxidants increase, promoting the oxidation of biomolecules. Among them, proteins are the major targets, due to their high biological abundance and reactivity towards one-and two-electron oxidants. [3][4][5] Protein residues most susceptible to oxidation are the sulfur-containing residues Cys and Met, and the aromatic residues His, Phe, Tyr, and Trp. In vivo, the oxidation of Cys and Met residues can be reversed by biological reductants with the assistance of enzymatic systems. In fact, the reversible oxidation of protein-Cys residues is emerging as a fundamental cell regulatory mechanism. 2,[6][7][8] The oxidation of all the other protein residues is irreversible, and includes several covalent modifications, such as protein cleavage, carbonylation, nitration, hydroxylation, halogenation and protein cross-linking with other proteins, lipids, carbohydrates and nucleic acids. [3][4][5][9][10][11] These modifications result in protein fragmentation, loss of protein function, protein aggregation and/or altered protein turnover, leading to cell and tissue dysfunction and various human pathologies. To maintain cellular homeostasis, proteins irreversibly oxidized are targeted for degradation by the proteasomal and lysosomal degradation pathways.11,12 During aging and pathological conditions associated with oxidative stress, however, the levels of over-oxidized and cross-linked proteins accumulate because these species are poor substrates for the intracellular proteolytic systems. This may lead to protein aggregation, which is a hallmark of age-related diseases, such as neurodegenerative diseases, atherosclerosis and cataract.11,12 Therefore, the study of irreversible protein oxidation in vitro and in vivo is relevant to the understanding o...

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“…Amino acid analysis by UPLC with fluorescence detection. Samples were prepared and subjected to acid hydrolysis using 4 M methanesulfonic acid as previously 29,30 . The resulting amino acid mixtures were subjected to pre-column derivatization using o-phthaldialdehyde and separated by UPLC with eluted materials detected by fluorescence (λ ex 340 nm, λ em 440 nm).…”

Section: Sds Gel Electrophoresis Protein Samples For Sds Gels Were Amentioning

confidence: 99%

UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites

Leinisch

Mariotti

Andersen

et al. 2020

Sci Rep

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UV light is a widely-employed, and environmentally-sensitive bactericide but its mechanism of action is not fully defined. Proteins are major chromophores and targets for damage due to their abundance, but the role of proteins in inducing damage to bound DNA, and the effects on DNA-protein interactions is less well characterized. in E. coli (and other Gram-negative bacteria) the cyclic AMp receptor protein (CRP/CAP) regulates more than 500 genes. In this study we show that exposure of isolated dimeric CRP-cAMP to UV modifies specific Met, Trp, Tyr, and Pro side-chains, induces inter-protein Tyr63-Tyr41 cross-links, and decreases DNA binding via oxidation of Met114/Pro110 residues in close proximity at the CRP dimer interface. UV exposure also modifies DNA-bound cAMP-CRP, with this resulting in DNA cleavage at specific G/C residues within the sequence bound to CRP, but not at other G/C sites. Oxidation also increases CRP dissociation from DNA. The modifications at the CRP dimer interface, and the sitespecific DNA strand cleavage are proposed to occur via oxidation of two species Met residues (Met114 and Met189, respectively) to reactive persulfoxides that damage neighbouring amino acids and DNA bases. These data suggest that modification to CRP, and bound DNA, contributes to UV sensitivity.The cyclic AMP receptor protein (CRP) (also known as the catabolite activator protein, CAP) is a global regulator of gene expression in E. coli and other Gram negative bacteria. CRP regulates more than 500 genes in E. coli by binding to approximately 300 high-affinity sites 1 . CRP also binds to more than 10000 low-affinity sites in the E. coli genome, indicating that CRP is not only a specific transcriptional regulator, but also a chromosome shaping protein 2,3 . CRP binds as a dimer to DNA sites, and subsequently with RNA polymerase to activate transcription. This activity is cAMP dependent, with complexation resulting in a conformational transition that converts apoCRP from a low-to a high-affinity DNA binding protein which binds at specific sequences upstream of the promoter 4 . The structural basis of CRP interactions with cAMP is well understood 5 . CRP is a homo-dimeric protein with each subunit able to bind one cAMP in a large N-terminal domain that is also responsible for subunit-subunit interactions 6,7 . A smaller C-terminal domain contains a helix-turn-helix motif involved in DNA attachment, with binding generating a strong kink in the DNA chain 8 . This CRP-DNA binding domain is highly conserved across many bacterial regulatory proteins 9,10 .Cell killing can also be readily induced by high energy radiation, UV and visible light in the presence of a sensitizer 11,12 . Proteins are both major UV absorbing species [13][14][15] , and major targets for oxidation due to their high abundance 16 . Trp, Tyr, Met, Cys, cystine and His side-chains are particularly prone to modification by UV light, or oxidants (e.g. singlet oxygen, 1 O 2 ) generated by energy transfer from other excited states 13,14,16 .We have therefore exam...

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Peroxyl radical- and photo-oxidation of glucose 6-phosphate dehydrogenase generates cross-links and functional changes via oxidation of tyrosine and tryptophan residues

Cited by 65 publications

References 84 publications

Effect of peroxyl radicals on the structure and gel properties of isolated rabbit meat myofibrillar proteins

Effect of peroxyl radicals on the structure and gel properties of isolated rabbit meat myofibrillar proteins

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites

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