Fasciola hepatica phosphoglycerate kinase (FhPGK) (FhPGK)

Fasciola hepatica phosphoglycerate kinase (FhPGK) is a key enzyme in the glycolytic pathway of the common liver fluke, a parasitic trematode that causes fascioliasis in humans and livestock (Front. Vet. Sci., 2020). It catalyzes the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, a step that generates ATP and is crucial for the parasite's energy metabolism (UniProt). Since the adult flukes live in the host's bile ducts, they depend significantly on glycolysis for their energy needs (Front. Vet. Sci., 2020). FhPGK has been validated as a therapeutic target, most notably for the drug clorsulon (MK-401), which is widely used in veterinary medicine (Mol. Biochem. Parasitol., 1982). Clorsulon acts as a competitive inhibitor of FhPGK, binding to the sites for both 3-phosphoglycerate and ATP, thereby disrupting the fluke's energy supply (Mol. Biochem. Parasitol., 1982). In addition to its role as a drug target, the enzyme is considered a promising vaccine candidate for preventing liver fluke infections (Front. Vet. Sci., 2020). A major challenge in targeting FhPGK is its structural similarity to the host's version of the enzyme, requiring high selectivity to avoid adverse effects in the host (Acta Parasitol., 2013). Research continues to focus on identifying novel inhibitors that can overcome resistance and provide effective treatment for both human and animal fascioliasis (Front. Vet. Sci., 2020).

Other names

PGK3-phosphoglycerate kinaseEC 2.7.2.3

Competitive inhibition of 3-phosphoglycerate and ATP binding sites