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

Georgios Kontellas; David J. Studholme; Mark van der Giezen; David J. Timson; Jennifer A. Littlechild; Michail N. Isupov

doi:10.1107/s2053230x25006454

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

Georgios Kontellas, David J. Studholme, Mark van der Giezen, David J. Timson, Jennifer A. Littlechild, Michail N. Isupov

School of Applied Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	381-387
Number of pages	7
Journal	Acta Crystallographica Section F
Volume	81
Issue number	9
DOIs	https://doi.org/10.1107/s2053230x25006454
Publication status	Published - 20 Aug 2025

Bibliographical note

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© 2025 International Union of Crystallography. All rights reserved.

Keywords

Fasciola hepatica
TIM
crystal structure
triclabendazole
TPI
triosephosphate isomerase

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title = "Triosephosphate isomerase from Fasciola hepatica: high‐resolution crystal structure as a drug target",

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 {\AA} 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.",

keywords = "Fasciola hepatica, TIM, crystal structure, triclabendazole, TPI, triosephosphate isomerase",

author = "Georgios Kontellas and Studholme, \{David J.\} and \{van der Giezen\}, Mark and Timson, \{David J.\} and Littlechild, \{Jennifer A.\} and Isupov, \{Michail N.\}",

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doi = "10.1107/s2053230x25006454",

language = "English",

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T2 - high‐resolution crystal structure as a drug target

AU - Kontellas, Georgios

AU - Studholme, David J.

AU - van der Giezen, Mark

AU - Timson, David J.

AU - Littlechild, Jennifer A.

AU - Isupov, Michail N.

PY - 2025/8/20

Y1 - 2025/8/20

N2 - 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.

AB - 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.

KW - Fasciola hepatica

KW - TIM

KW - crystal structure

KW - triclabendazole

KW - TPI

KW - triosephosphate isomerase

UR - https://www.scopus.com/pages/publications/105014762932

U2 - 10.1107/s2053230x25006454

DO - 10.1107/s2053230x25006454

M3 - Article

SN - 2053-230X

VL - 81

SP - 381

EP - 387

JO - Acta Crystallographica Section F

JF - Acta Crystallographica Section F

IS - 9

ER -

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

Abstract

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Keywords

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