@article{8830b7ac9a844999aa02a1cbb790711e,
title = "Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling?",
abstract = "The reversible oxidation of protein cysteine residues (Cys-SH) is a key reaction in cellular redox signaling involving initial formation of sulfenic acids (Cys-SOH), which are commonly detected using selective dimedone-based probes. Here, we report that significant portions of dimedone-tagged proteins are susceptible to cleavage by DTT reflecting the presence of perthiosulfenic acid species (Cys-SSOH) due to similar oxidation of hydropersulfides (Cys-SSH), since Cys-S-dimedone adducts are stable toward DTT. Combined studies using molecular modeling, mass spectrometry, and cell-based experiments indicate that Cys-SSH are readily oxidized to Cys-SSOH, which forms stable adducts with dimedone-based probes. We additionally confirm the presence of Cys-SSH within protein tyrosine kinases such as EGFR, and their apparent oxidation to Cys-SSOH in response NADPH oxidase activation, suggesting that such Cys-SSH oxidation may represent a novel, as yet uncharacterized, event in redox-based signaling.",
keywords = "Dimedone, Hydrogen peroxide, NADPH oxidase, Redox signaling, Sulfenic acid, Thiol oxidation",
author = "Heppner, {David E.} and Milena Hristova and Tomoaki Ida and Ana Mijuskovic and Dustin, {Christopher M.} and Vir{\'a}g Bogd{\'a}ndi and Fukuto, {Jon M.} and Dick, {Tobias P.} and P{\'e}ter Nagy and Jianing Li and Takaaki Akaike and {van der Vliet}, Albert",
note = "Funding Information: The authors gratefully acknowledge the following sources of research support: National Institutes of Health Grants R01HL085646 and ES021476 to AvdV; Fellowship F32 HL129706 to DEH; Grants-in-Aid for Scientific Research from the Ministry of Education, Sciences, Sports, and Technology (MEXT), Japan , to TA ( 26111008, 26111001, 15K21759, 25253020, 16K15208 ); and research grants from the Deutsche Forschungsgemeinschaft (DFG; grant SFB1036 to TPD) and the Hungarian National Science Foundation (OTKA; grant No.: K109843 to PN). Computational resources were provided to JL by Vermont Advanced Computing Core (VACC) and Stampede from the Extreme Science and Engineering Discovery Environment (XSEDE, NSF Grant No. ACI-1053575 ). The authors also thank Dr. Christopher J. Cramer for helpful discussions and comments. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2018",
month = apr,
doi = "10.1016/j.redox.2017.10.006",
language = "English",
volume = "14",
pages = "379--385",
journal = "Redox Biology",
issn = "2213-2317",
publisher = "Elsevier BV",
}