Identification of novel S-nitrosation sites in soluble guanylyl cyclase, the nitric oxide receptor

Annie Beuve, Changgong Wu, Chuanlong Cui, Tong Liu, Mohit Raja Jain, Can Huang, Lin Yan, Vladyslav Kholodovych, Hong Li

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Soluble Guanylyl Cyclase (sGC) is the main receptor for nitric oxide (NO). NO activates sGC to synthesize cGMP, triggering a plethora of signals. Recently, we discovered that NO covalently modifies select sGC cysteines via a post-translational modification termed S-nitrosation or S-nitrosylation. Earlier characterization was conducted on a purified sGC treated with S-nitrosoglutathione, and identified three S-nitrosated cysteines (SNO-Cys). Here we describe a more biologically relevant mapping of sGC SNO-Cys in cells to better understand the multi-faceted interactions between SNO and sGC. Since SNO-Cys are labile during LC/MS/MS, MS analysis of nitrosation typically occurs after a biotin switch reaction, in which a SNO-Cys is converted to a biotin-Cys. Here we report the identification of ten sGC SNO-Cys in rat neonatal cardiomyocytes using an Orbitrap MS. A majority of the SNO-Cys identified is located at the solvent-exposed surface of the sGC, and half of them in the conserved catalytic domain, suggesting biological significance. These findings provide a solid basis for future studies of the regulations and functions of diverse sGC S-nitrosation events in cells.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalJournal of Proteomics
StatePublished - Apr 14 2016

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry


  • Biotin switch
  • S-nitrosation
  • Soluble guanylyl cyclase
  • Tandem mass spectrometry


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