Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of GST family

EMBO Rep. 2009 Dec;10(12):1320-6. doi: 10.1038/embor.2009.216. Epub 2009 Oct 23.


Glutathione-S-transferases (GSTs) are ubiquitous detoxification enzymes that catalyse the conjugation of electrophilic substrates to glutathione. Here, we present the crystal structures of Gtt2, a GST of Saccharomyces cerevisiae, in apo and two ligand-bound forms, at 2.23 A, 2.20 A and 2.10 A, respectively. Although Gtt2 has the overall structure of a GST, the absence of the classic catalytic essential residues--tyrosine, serine and cysteine--distinguishes it from all other cytosolic GSTs of known structure. Site-directed mutagenesis in combination with activity assays showed that instead of the classic catalytic residues, a water molecule stabilized by Ser129 and His123 acts as the deprotonator of the glutathione sulphur atom. Furthermore, only glycine and alanine are allowed at the amino-terminus of helix-alpha1 because of stereo-hindrance. Taken together, these results show that yeast Gtt2 is a novel atypical type of cytosolic GST.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Crystallography, X-Ray
  • Cytosol / enzymology
  • Cytosol / metabolism
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / metabolism
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid


  • Mutant Proteins
  • Glutathione Transferase