Structural and biochemical characterization of yeast monothiol glutaredoxin Grx6

J Mol Biol. 2010 May 14;398(4):614-22. doi: 10.1016/j.jmb.2010.03.029. Epub 2010 Mar 27.


Glutaredoxins (Grxs) are a ubiquitous family of proteins that reduce disulfide bonds in substrate proteins using electrons from reduced glutathione (GSH). The yeast Saccharomyces cerevisiae Grx6 is a monothiol Grx that is localized in the endoplasmic reticulum and Golgi compartments. Grx6 consists of three segments, a putative signal peptide (M1-I36), an N-terminal domain (K37-T110), and a C-terminal Grx domain (K111-N231, designated Grx6C). Compared to the classic dithiol glutaredoxin Grx1, Grx6 has a lower glutathione disulfide reductase activity but a higher glutathione S-transferase activity. In addition, similar to human Grx2, Grx6 binds GSH via an iron-sulfur cluster in vitro. The N-terminal domain is essential for noncovalent dimerization, but not required for either of the above activities. The crystal structure of Grx6C at 1.5 A resolution revealed a novel two-strand antiparallel beta-sheet opposite the GSH binding groove. This extra beta-sheet might also exist in yeast Grx7 and in a group of putative Grxs in lower organisms, suggesting that Grx6 might represent the first member of a novel Grx subfamily.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Glutaredoxins / chemistry*
  • Glutaredoxins / metabolism*
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment


  • Glutaredoxins
  • Grx6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Glutathione
  • Glutathione Disulfide

Associated data

  • PDB/3L4N