Sigma-Class Glutathione Transferases (GSTσ): A New Target with Potential for Helminth Control

Abstract

Glutathione transferases (GSTs EC 2.5.1.18) are critical components of phase II metabolism, instrumental in xenobiotics' metabolism. Their primary function involves conjugating glutathione to both endogenous and exogenous toxic compounds, which increases their solubility and enables their ejection from cells. They also play a role in the transport of non-substrate compounds and immunomodulation, aiding in parasite establishment within its host. The cytosolic GST subfamily is the most abundant and diverse in helminths, and sigma-class GST (GSTσ) belongs to it. This review focuses on three key functions of GSTσ: serving as a detoxifying agent that provides drug resistance, functioning as an immune system modulator through its involvement in prostaglandins synthesis, and acting as a vaccine antigen.

Keywords: GST sigma; antigens; helminths; prostaglandin; resistance; vaccination.

Figure 1

(A) Identification of the G (yellow) and H (blue) sites and a third site with the potential to transport non-substrate compounds (green). (B) Superposition of three crystallographic structures of GSTσ, where the conservation of Tyr is observed as the residue responsible for activating the thiol group of GSH (2GSQ.pdb (green), GSTσ in squid; 2WB9.pdb (magenta), FhGST-S1; 3VPQ.pdb (blue), and bmGST1.