Protein S-thiolation by glutathionylspermidine (Gsp): The role of Escherichia coli Gsp synthetase/amidase in redox regulation

Bing Yu Chiang, Tzu Chieh Chen, Chien Hua Pai, Chi Chi Chou, Hsuan He Chen, Tzu Ping Ko, Wen Hung Hsu, Chun Yang Chang, Whei Fen Wu, Andrew H.J. Wang, Chun Hung Lin

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Certain bacteria synthesize glutathionylspermidine (Gsp), from GSH and spermidine. Escherichia coli Gsp synthetase/amidase (GspSA) catalyzes both the synthesis and hydrolysis of Gsp. Prior to the work reported herein, the physiological role(s) of Gsp or how the two opposing GspSA activities are regulated had not been elucidated. We report that Gsp-modified proteins from E. coli contain mixed disulfides of Gsp and protein thiols, representing a new type of post-translational modification formerly undocumented. The level of these proteins is increased by oxidative stress. We attribute the accumulation of such proteins to the selective inactivation of GspSA amidase activity. X-ray crystallography and a chemical modification study indicated that the catalytic cysteine thiol of the GspSA amidase domain is transiently inactivated byH 2O2 oxidation to sulfenic acid, which is stabilized by a very short hydrogen bond with a water molecule. We propose a set of reactions that explains how the levels of Gsp and Gsp S-thiolated proteins are modulated in response to oxidative stress. The hypersensitivities of GspSA and GspSA/glutaredoxin null mutants toH2O2 support the idea that GspSA and glutaredoxin act synergistically to regulate the redox environment of E. coli.

Original languageEnglish
Pages (from-to)25345-25353
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number33
DOIs
Publication statusPublished - Aug 13 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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