Comparative analyses and structural insights of new class glutathione transferases in Cryptosporidium species

Mbalenhle Sizamile Mfeka1, José Martínez-Oyanedel2, Wanping Chen3

  • 1Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal (Pietermaritzburg Campus), Scottsville, Pietermaritzburg, KwaZulu-Natal, 3209, South Africa.

Scientific Reports
|November 24, 2020
PubMed

Insights

This study identifies and classifies glutathione transferases (GSTs) in fifteen Cryptosporidium species, revealing three novel GST classes (Vega, Gamma, Psi) and potential drug targets for cryptosporidiosis, a major parasitic disease.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cryptosporidiosis is a leading neglected zoonotic parasitic disease and a major cause of childhood mortality.
  • Glutathione transferases (GSTs) in Cryptosporidium parvum are potential drug targets due to their role in pathogen survival.
  • A comprehensive understanding of GSTs across Cryptosporidium species is lacking.

Purpose of the Study:

  • To perform a genome-wide analysis of GSTs in fifteen Cryptosporidium species.
  • To classify and structurally analyze these GSTs.
  • To identify potential drug targets for cryptosporidiosis.

Main Methods:

  • Genome-wide data mining and identification of GSTs.
  • In silico structural and phylogenetic analysis.
  • Comparative analysis of GSTs across fifteen Cryptosporidium species.

Main Results:

  • Three GSTs were identified in each analyzed Cryptosporidium species.
  • Three novel GST classes, Vega (ϑ), Gamma (γ), and Psi (ψ), were established based on phylogenetic analysis.
  • Distinct structural features, including atypical thioredoxin-like folds, were observed in specific C. parvum and C. melagridis GSTs.

Conclusions:

  • This study provides the first comparative analysis of GSTs in Cryptosporidium species.
  • The identified GSTs and their structural characteristics offer new insights for developing anti-cryptosporidial drugs.
  • The novel Vega, Gamma, and Psi GST classes represent important targets for therapeutic intervention against cryptosporidiosis.

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