Triosephosphate isomerase from Fasciola hepatica: high-resolution crystal structure as a drug target.

Acta Crystallogr F Struct Biol Commun

Henry Wellcome Building for Biocatalysis, Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom.

Published: September 2025


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Article Abstract

The trematode liver fluke Fasciola hepatica causes the neglected tropical disease fascioliasis in humans and is associated with significant losses in agricultural industry due to reduced animal productivity. Triosephosphate isomerase (TPI) is a glycolytic enzyme that has been researched as a drug target for various parasites, including F. hepatica. The high-resolution crystal structure of F. hepatica TPI (FhTPI) has been solved at 1.51 Å resolution in its monoclinic form. The structure has been used to perform molecular-docking studies with the most successful fasciolocide triclabendazole (TCBZ), which has recently been suggested to target FhTPI. Two FhTPI residues, Lys50 and Asp51, are located at the dimer interface and are found in close proximity to the docked TCBZ. These residues are not conserved in mammalian hosts.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400196PMC
http://dx.doi.org/10.1107/S2053230X25006454DOI Listing

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Triosephosphate isomerase (TPI) is a ubiquitously expressed enzyme encoded by the TPI1 gene. It catalyzes the interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in the fifth step of glycolysis. TPI deficiency (TPI Df; MIM# 615512) is an autosomal recessive disorder due to biallelic pathogenic variants in TPI1.

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