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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
14:57

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

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

Markus Perbandt1, Jana Höppner, Christian Betzel

  • 1Institute of Biochemistry and Foodchemistry, Department of Biochemistry and Molecularbiology, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, Germany. Perbandt@chemie.uni-hamburg.de

The Journal of Biological Chemistry
|January 11, 2005
PubMed

Insights

Onchocerciasis, a parasitic disease, is fought by targeting glutathione S-transferases (GSTs). Researchers elucidated the structure of Onchocerca volvulus GST2 (Ov-GST2), revealing unique features for drug development.

Area of Science:

  • Parasitology
  • Structural Biology
  • Biochemistry

Background:

  • Onchocerciasis, caused by Onchocerca volvulus, is a debilitating parasitic disease.
  • Onchocerca volvulus evades host immunity using mechanisms like glutathione S-transferases (GSTs).
  • GSTs are upregulated during drug treatment, making them targets for chemotherapy and vaccine development.

Purpose of the Study:

  • To analyze the 3D x-ray structure of the major cytosolic GST from O. volvulus (Ov-GST2).
  • To understand the structural basis for Ov-GST2's function and substrate specificity.
  • To provide insights for parasite-specific drug design against onchocerciasis.

Main Methods:

  • X-ray crystallography was used to determine the structure of Ov-GST2.
  • The structure was analyzed in complex with glutathione and S-hexylglutathione.
  • Structural comparisons were made with other pi-class GSTs, including human counterparts.

Main Results:

  • The 3D x-ray structure of Ov-GST2 was determined at 1.5 and 1.8 angstrom resolution.
  • Ov-GST2, while related to pi-class GSTs, exhibits significant structural differences from host GSTs.
  • Key differences were identified in helix alpha-2 and the co-substrate binding site, leading to altered substrate specificities.

Conclusions:

  • Ov-GST2 possesses unique structural features that differentiate it from host GSTs.
  • These structural variations offer opportunities for developing parasite-specific inhibitors.
  • The findings support structure-based drug design for novel onchocerciasis treatments.

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