Thioredoxin-like domain of human kappa class glutathione transferase reveals sequence homology and structure similarity to the theta class enzyme

Protein Sci. 2005 Sep;14(9):2361-9. doi: 10.1110/ps.051463905. Epub 2005 Aug 4.

Abstract

Glutathione transferases (GSTs) are a superfamily of enzymes that play a vital functional role in the cellular detoxification process. They catalyze the conjugation of the thiol group of glutathione (GSH) to the electrophilic groups of a wide range of hydrophobic substrates, leading to an easier removal of the latter from the cells. The kappa class is the least studied one among various classes within the superfamily. We report here the expression, purification, and crystal structure of human kappa class GST (hGSTK), which has been determined by the multiple-isomorphous replacement method and refined to 1.93 A resolution. The overall structure of hGSTK is similar to the recently reported structure of kappa class GST from rat mitochondrion. Each subunit of the dimeric hGSTK contains a thioredoxin (TRX)-like domain and a helical domain. A molecule of glutathione sulfinate, an oxidized product of GSH, is found to bind at the G site of each monomer. One oxygen atom of the sulfino group of GSF forms a hydrogen bond with the hydroxyl group of the catalytic residue Ser16. The TRX-like domain of hGSTK shares 19% sequence identity and structure similarity with human theta class GST, suggesting that the kappa class of GST is more closely related to the theta class enzyme within the GST superfamily. The structure of the TRX-like domain of hGSTK is also similar to that of glutathione peroxidase (GPx), implying an evolutionary relationship between GST and GPx.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Glutathione Peroxidase / chemistry
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Structural Homology, Protein
  • Thioredoxins / chemistry*

Substances

  • Thioredoxins
  • Glutathione Peroxidase
  • GSTK1 protein, human
  • Glutathione Transferase

Associated data

  • PDB/1YZX