Structure of the major cytosolic glutathione S-transferase from the parasitic nematode Onchocerca volvulus

J Biol Chem. 2005 Apr 1;280(13):12630-6. doi: 10.1074/jbc.M413551200. Epub 2005 Jan 7.


Onchocerciasis is a debilitating parasitic disease caused by the filarial worm Onchocerca volvulus. Similar to other helminth parasites, O. volvulus is capable of evading the host's immune responses by a variety of defense mechanisms, including the detoxification activities of the glutathione S-transferases (GSTs). Additionally, in response to drug treatment, helminth GSTs are highly up-regulated, making them tempting targets both for chemotherapy and for vaccine development. We analyzed the three-dimensional x-ray structure of the major cytosolic GST from O. volvulus (Ov-GST2) in complex with its natural substrate glutathione and its competitive inhibitor S-hexylglutathione at 1.5 and 1.8 angstrom resolution, respectively. From the perspective of the biochemical classification, the Ov-GST2 seems to be related to pi-class GSTs. However, in comparison to other pi-class GSTs, in particular to the host's counterpart, the Ov-GST2 reveals significant and unusual differences in the sequence and overall structure. Major differences can be found in helix alpha-2, an important region for substrate recognition. Moreover, the binding site for the electrophilic co-substrate is spatially increased and more solvent-accessible. These structural alterations are responsible for different substrate specificities and will form the basis of parasite-specific structure-based drug design investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Cytosol / enzymology*
  • Cytosol / metabolism
  • Escherichia coli / metabolism
  • Glutathione / analogs & derivatives*
  • Glutathione / chemistry
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Onchocerca volvulus / enzymology*
  • Onchocerca volvulus / metabolism
  • Placenta / enzymology
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Up-Regulation


  • Glutathione Transferase
  • Glutathione
  • hexylglutathione

Associated data

  • PDB/1TU7
  • PDB/1TU8