Parasit Host Dis.  2024 May;62(2):205-216. 10.3347/PHD.24004.

Prostaglandin synthase activity of sigma- and mu-class glutathione transferases in a parasitic trematode, Clonorchis sinensis

• Kim J
• Sohn WM
• Bae YA

• KMID: 2556158
• DOI: http://doi.org/10.3347/PHD.24004

Abstract

Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-μ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D₂ synthases. Recombinant forms of these CsGST-σ and CsGST-μ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H₂ (PGS substrate; average Km of 30.7 and 3.0 μm for prostaglandin D₂ [PGDS] and E₂ synthase [PGES], respectively) than those toward CDNB (GST substrate; average K_m of 1,205.1 μm). Furthermore, the catalytic efficiency (K_cat/K_m) of the PGDS/PGES activity was higher than that of GST activity (average K_cat/K_m of 3.1, 0.7, and 7.0×10^-3 s^-1μm^-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD₂ and PGE₂ in addition to their roles in general detoxification.

Keyword

Glutathione transferase; prostaglandin; prostaglandin D₂ synthase; prostaglandin E₂ synthase; Clonorchis sinensis; steady-state kinetic analysis