Nitrosothiosulphate ion (S2O3NO–) as a nitrosating species

Bryant, Tracey; Williams, D. Lyn H.; Ali, Mohsin; Stedman, Geoffrey

doi:10.1039/p29860000193

Cited by 6 publications

(2 citation statements)

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“…We hypothesized that SNO-bearing substrates or substrate mimetics might serve as inhibitors of these enzymes. SNO-thiosulfate is unstable (33), but a previously unidentified phospho-tyrosine mimetic, S-nitroso-4-mercaptophenylacetic acid (PASNO; Fig. S4) inhibited and S-nitrosylated Ych1p (Figs.…”

Section: Resultsmentioning

confidence: 99%

A protein microarray-based analysis of S -nitrosylation

Foster

Forrester

Stamler

2009

Proc. Natl. Acad. Sci. U.S.A.

104

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The ubiquitous cellular influence of nitric oxide (NO) is exerted substantially through protein S-nitrosylation. Whereas NO is highly promiscuous, physiological S-nitrosylation is typically restricted to one or very few Cys residue(s) in target proteins. The molecular basis for this specificity may derive from properties of the target protein, the S-nitrosylating species, or both. Here, we describe a protein microarray-based approach to investigate determinants of S-nitrosylation by biologically relevant low-mass S-nitrosothiols (SNOs). We identify large sets of yeast and human target proteins, among which those with active-site Cys thiols residing at N termini of ␣-helices or within catalytic loops were particularly prominent. However, S-nitrosylation varied substantially even within these families of proteins (e.g., papain-related Cys-dependent hydrolases and rhodanese/Cdc25 phosphatases), suggesting that neither secondary structure nor intrinsic nucleophilicity of Cys thiols was sufficient to explain specificity. Further analyses revealed a substantial influence of NO-donor stereochemistry and structure on efficiency of S-nitrosylation as well as an unanticipated and important role for allosteric effectors. Thus, high-throughput screening and unbiased proteome coverage reveal multifactorial determinants of S-nitrosylation (which may be overlooked in alternative proteomic analyses), and support the idea that target specificity can be achieved through rational design of S-nitrosothiols.cysteine ͉ nitric oxide ͉ S-nitrosothiol ͉ thiol P rotein S-nitrosylation underlies much of the physiological signaling by both nitric oxide (NO) and endogenous Snitrosothiols, and both hypo-and hyper-S-nitrosylation have been causally implicated in disease (1, 2). Formally, Snitrosylation occurs either via an oxidative reaction of NO and Cys thiol, in the presence of an electron acceptor (e.g., transition metal or O 2 ), or by the transfer of NO ϩ (transnitros(yl)ation) from donor S-nitrosothiol (SNO) to acceptor Cys thiol (1). These reactions may be enzyme-catalyzed or otherwise facilitated. For example, hemoglobin and ceruloplasmin support metaldependent S-nitrosylation (3-5) whereas S-nitroso-hemoglobin (SNO-hemoglobin) and SNO-thioredoxin can transnitrosylate proteins with which they interact directly (anion exchanger 1 and caspase-3, respectively) (6, 7). Transnitrosylation is also implicated in protein S-nitrosylation coupled to NO synthase activity (8-10) and involves the intermediacy of the endogenous lowmass SNO, S-nitrosoglutathione (GSNO), as evidenced by elevated levels of SNO-proteins in mice lacking the GSNO metabolizing enzyme, GSNO reductase (GSNOR) (8-11). GSNOR deletion also increases S(NO)-mediated protein S-nitrosylation and cytostasis in yeast (11,12), and decreases virulence of several pathogens (13, 14), which suggests that transnitrosylation is an important mediator of nitrosative stress. In addition, metabolism of GSNO to S-nitrosocyteinylglycine and S-nitrosocysteine (CysNO) and CysNO uptake via l-amino...

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Section: Resultsmentioning

confidence: 99%

A protein microarray-based analysis of S -nitrosylation

Foster

Forrester

Stamler

2009

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

show abstract

“…This happens also with S 2 O 3 2Ϫ as a catalyst at all concentrations since K NOX is so large (1.67 × 10 7 dm 6 mol Ϫ2 ). However the negatively charged S-nitroso ion is not a very efficient nitrosating agent, 28 and so overall S 2 O 3 2Ϫ is not such an efficient catalyst as is thiourea for example.…”

Section: Sno ؉ As a Nitrosating Speciesmentioning

confidence: 99%