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Updated: Jul 7, 2026

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 extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca

Markus Perbandt1, Jana Höppner, Cora Burmeister

  • 1Institute of Biochemistry, Center for Structural and Cell Biology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. perbandt@biochem.uni-luebeck.de

Journal of Molecular Biology
|February 9, 2008
PubMed

Insights

Onchocerca volvulus glutathione S-transferase 1 (OvGST1) is crucial for river blindness pathogenesis. Its unique structure and function as a prostaglandin D synthase (PGDS) offer new therapeutic targets for this infectious blinding disease.

Area of Science:

  • Parasitology
  • Structural Biology
  • Immunology

Background:

  • Onchocerciasis, or river blindness, is a major cause of infectious blindness globally, caused by the filarial worm Onchocerca volvulus.
  • O. volvulus employs molecular strategies to evade host immune responses during chronic infection.
  • The O. volvulus glutathione S-transferase 1 (OvGST1) is a unique secreted glycoprotein functioning as a prostaglandin D synthase (PGDS) at the parasite-host interface.

Purpose of the Study:

  • To elucidate the crystal structure of OvGST1 bound to its cofactor glutathione.
  • To understand the structural basis for OvGST1's function as a PGDS.
  • To identify potential targets for anti-parasitic chemotherapy and vaccine development.

Main Methods:

  • X-ray crystallography was used to determine the OvGST1-glutathione complex structure at 2.0 Å resolution.

Main Results:

  • The crystal structure revealed homology to vertebrate haematopoietic PGDS but with significant conformational changes in the prostaglandin binding pocket.
  • These differences suggest a distinct binding mode for prostaglandin H(2) compared to vertebrate PGDS.
  • A putative substrate binding mode for prostaglandin H(2) was proposed based on the structural findings.

Conclusions:

  • OvGST1's unique structure and PGDS activity highlight its role in modulating host immune responses.
  • The structural insights provide a foundation for designing novel therapeutics against Onchocerciasis.
  • OvGST1 represents a promising target for developing new treatments and vaccines for river blindness.

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