Kontellas Georgios, Studholme David J, van der Giezen Mark, Timson David J, Littlechild Jennifer A, Isupov Michail N
Henry Wellcome Building for Biocatalysis, Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom.
Biosciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom.
Acta Crystallogr F Struct Biol Commun. 2025 Sep 1;81(Pt 9):381-387. doi: 10.1107/S2053230X25006454. Epub 2025 Aug 20.
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.
吸虫肝片吸虫可导致人类感染被忽视的热带疾病肝片吸虫病，并且由于动物生产力下降而给农业产业造成重大损失。磷酸丙糖异构酶（TPI）是一种糖酵解酶，已作为包括肝片吸虫在内的各种寄生虫的药物靶点进行研究。肝片吸虫TPI（FhTPI）的高分辨率晶体结构已以单斜晶形式在1.51 Å分辨率下解析出来。该结构已用于与最成功的杀肝片吸虫药三氯苯达唑（TCBZ）进行分子对接研究，最近有人提出TCBZ的靶点是FhTPI。FhTPI的两个残基Lys50和Asp51位于二聚体界面，且发现它们与对接的TCBZ非常接近。这些残基在哺乳动物宿主中并不保守。
