Mechanism of 1-Cys type methionine sulfoxide reductase A regeneration by glutaredoxin

Moon Jung Kim, Jaeho Jeong, Jihye Jeong, Kwang Yeon Hwang, Kong Joo Lee, Hwa Young Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Glutaredoxin (Grx), a major redox regulator, can act as a reductant of methionine sulfoxide reductase A (MsrA). However, the biochemical mechanisms involved in MsrA activity regeneration by Grx remain largely unknown. In this study, we investigated the regeneration mechanism of 1-Cys type Clostridium oremlandii MsrA (cMsrA) lacking a resolving Cys residue in a Grx-dependent assay. Kinetic analysis showed that cMsrA could be reduced by both monothiol and dithiol Grxs as efficiently as by in vitro reductant dithiothreitol. Our data revealed that the catalytic Cys sulfenic acid intermediate is not glutathionylated in the presence of the substrate, and that Grx instead directly formed a complex with cMsrA. Mass spectrometry analysis identified a disulfide bond between the N-terminal catalytic Cys of the active site of Grx and the catalytic Cys of cMsrA. This mixed disulfide bond could be resolved by glutathione. Based on these findings, we propose a model for regeneration of 1-Cys type cMsrA by Grx that involves no glutathionylation on the catalytic Cys of cMsrA. This mechanism contrasts with that of the previously known 1-Cys type MsrB.

Original languageEnglish
Pages (from-to)567-571
Number of pages5
JournalBiochemical and biophysical research communications
Issue number4
Publication statusPublished - 2015 Feb 20

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea ( 2011-0028166 and 2014R1A1A2057525 ) and Global Research Lab Program ( 2012K1A1A2045441 ).

Publisher Copyright:
© 2015 Elsevier Inc.


  • 1-Cys
  • Disulfide bond
  • Glutaredoxin
  • Glutathionylation
  • MsrA
  • Regeneration

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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