Structural Features of Proteins Responsible for Resistance of Tryptophan Residues to Nitrosylation

Suntsova, Tatiana P.; Nedospasov, A. A.

doi:10.1080/15216540215677

Cited by 15 publications

(11 citation statements)

References 33 publications

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“…S-, C-, and N-Nitrosylation While S-nitrosylation and the formation of R-S-nitrosothiols are well documented, the formation of N-nitrosoamines [44], which also occurs in vivo, is perhaps under discussed [45,46]. This process is often described as N-nitrosylation [45,46].…”

Section: Homeostatic Regulation Of Nitrosylationmentioning

confidence: 96%

“…N 2 O 3 is also likely to be the nitrosylation agent in the formation of nitroso-tyrosine [52,53] and nitroso-tryptophan [52]. The formation of nitroso-tryptophan is particularly representative of excessive nitrosative stress, as tryptophan is highly resistant to nitrosylation [46,54]. There is considerable evidence that nitroxyl molecules (NO − ) can attack electropositive cysteine thiol groups, which is the mechanism underpinning SNO of the N-methyl-D-aspartate (NMDA) receptor [55,56].…”

Section: Homeostatic Regulation Of Nitrosylationmentioning

confidence: 99%

“…There is yet another type of nitrosylation, described as Cnitrosylation, where the carbon center acts as the electrophilic acceptor [46]. SNO of cysteine thiol groups can generally be achieved via one of different alternative mechanisms.…”

Section: Homeostatic Regulation Of Nitrosylationmentioning

confidence: 99%

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Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Morris¹,

Berk

Klein

et al. 2016

Mol Neurobiol

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Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

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Section: Homeostatic Regulation Of Nitrosylationmentioning

confidence: 96%

Section: Homeostatic Regulation Of Nitrosylationmentioning

confidence: 99%

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Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Morris¹,

Berk

Klein

et al. 2016

Mol Neurobiol

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“…This issue was previously conceptualized with regard to Trp nitrosation and should also be considered as far as protein RNNO denitrosation is concerned [37].…”

Section: Discussionmentioning

confidence: 99%

Redox-Sensitivity and Site-Specificity of S- and N- Denitrosation in Proteins

et al. 2010

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BackgroundS-nitrosation – the formation of S-nitrosothiols (RSNOs) at cysteine residues in proteins – is a posttranslational modification involved in signal transduction and nitric oxide (NO) transport. Recent studies would also suggest the formation of N-nitrosamines (RNNOs) in proteins in vivo, although their biological significance remains obscure. In this study, we characterized a redox-based mechanism by which N-nitroso-tryptophan residues in proteins may be denitrosated.Methodology/Principal FindingsThe denitrosation of N-acetyl-nitroso Trp (NANT) by glutathione (GSH) required molecular oxygen and was inhibited by superoxide dismutase (SOD). Transnitrosation to form S-nitrosoglutathione (GSNO) was observed only in the absence of oxygen or presence of SOD. Protein denitrosation by GSH was studied using a set of mutant recombinant human serum albumin (HSA). Trp-214 and Cys-37 were the only two residues nitrosated by NO under aerobic conditions. Nitroso-Trp-214 in HSA was insensitive to denitrosation by GSH or ascorbate while denitrosation at Cys-37 was evident in the presence of GSH but not ascorbate. GSH-dependent denitrosation of Trp-214 was restored in a peptide fragment of helix II containing Trp-214. Finally, incubation of cell lysates with NANT revealed a pattern of protein nitrosation distinct from that observed with GSNO.ConclusionsWe propose that the denitrosation of nitrosated Trp by GSH occurs through homolytic cleavage of nitroso Trp to NO and a Trp aminyl radical, driven by the formation of superoxide derived from the oxidation of GSH to GSSG. Overall, the accessibility of Trp residues to redox-active biomolecules determines the stability of protein-associated nitroso species such that in the case of HSA, N-nitroso-Trp-214 is insensitive to denitrosation by low-molecular-weight antioxidants. Moreover, RNNOs can generate free NO and transfer their NO moiety in an oxygen-dependent fashion, albeit site-specificities appear to differ markedly from that of RSNOs.

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“…These include spatial buffering and redistribution of NO and nitrite in organisms via reversible interaction with circulatory proteins and cells [30,91]. For example, NO may interact with haem-binding proteins in erythrocytes [26,92,93], other metal-binding proteins of cells and plasma [94,95], as well as with sulfhydryl (R-SH) and aromatic (R, indole or phenol) [96][97][98] groups of proteins, biopolymers and free amino acids (see also above).…”

Section: 13mentioning

confidence: 99%

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

Boudko

2007

Journal of Chromatography B

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This review briefly summarizes recent progress in fundamental understanding and analytical profiling of the L-arginine/nitric oxide (NO) pathway. It focuses on key analytical references of NO actions and on the experimental acquisition of these references in vivo, with capillary electrophoresis (CE) and high-performance capillary electrophoresis (HPCE) comprising one of the most flexible and technologically promising analytical platform for comprehensive high-resolution profiling of NO-related metabolites. Second aim of this review is to express demands and bridge efforts of experimental biologists, medical professionals and chemical analysis-oriented scientists who strive to understand evolution and physiological roles of NO and to develop analytical methods for use in biology and medicine.

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Structural Features of Proteins Responsible for Resistance of Tryptophan Residues to Nitrosylation

Abstract: SummaryIt is known that potentially reactive groups of the protein molecule may be most efficiently nitros(yl)ated only when located within hydrophobic globules or built into the membrane.

Cited by 15 publications

References 33 publications

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Redox-Sensitivity and Site-Specificity of S- and N- Denitrosation in Proteins

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

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