Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reversible chemical modifications of protein cysteine residues by S-nitrosylation and S-oxidation are increasingly recognized as important regulatory mechanisms for many protein classes associated with cellular signaling and stress response. Both modifications may theoretically occur under cellular nitrosative or nitroxidative stress. Therefore, a proteomic isotope-coded approach to parallel, quantitative analysis of cysteome S-nitrosylation and S-oxidation was developed. Modifications of cysteine residues of (i) human glutathione-S-transferase P1-1 (GSTP1) and (ii) the schistosomiasis drug target thioredoxin glutathione reductase (TGR) were studied. Both S-nitrosylation (SNO) and S-oxidation to disulfide (SS) were observed for reactive cysteines, dependent on concentration of added S-nitrosocysteine (CysNO) and independent of oxygen. SNO and SS modifications of GSTP1 were quantified and compared for therapeutically relevant NO and HNO donors from different chemical classes, revealing oxidative modification for all donors. Observations on GSTP1 were extended to cell cultures, analyzed after lysis and in-gel digestion. Treatment of living neuronal cells with CysNO, to induce nitrosative stress, caused levels of S-nitrosylation and S-oxidation of GSTP1 comparable to those of cell-free studies. Cysteine modifications of PARK7/DJ-1, peroxiredoxin-2, and other proteins were identified, quantified, and compared to overall levels of protein S-nitrosylation. The new methodology has allowed identification and quantitation of specific cysteome modifications, demonstrating that nitroxidation to protein disulfides occurs concurrently with S-nitrosylation to protein-SNO in recombinant proteins and living cells under nitrosative stress.
ACS Chem Biol 2014 Mar 21
PMID:Proteomic profiling of nitrosative stress: protein S-oxidation accompanies S-nitrosylation. 2439 69

Species of the blood fluke Schistosoma are responsible for schistosomiasis, the second most common parasitic disease, which is prevalent particularly in poor communities. Under redox pressure, schistosomes survive in mammalian hosts with the help of thioredoxin glutathione reductase, which is an essential selenoenzyme. A recent study identified compounds with extremely potent antischistosome activity. Most importantly, certain compounds were active against all major schistosomes across different life cycle stages, where even praziquantel, the drug of choice, fails. The data offer compounds that exceed WHO standards for leads for schistosomiasis therapy activity. The work may serve as the basis for the development of new antischistosome compounds.
ACS Infect Dis 2020 05 08
PMID:Potent Inhibitors of Thioredoxin Glutathione Reductase: Grail of Anti-Schistosome Drug within Reach? 3215 29