# Structural insights into sigma class glutathione transferase from Taenia solium: Analysis and functional implications

## TL;DR

This study reveals the structure of a key enzyme from a parasite causing neurocysticercosis, offering insights into its function and potential for new treatments.

## Contribution

The first crystallographic structures of a sigma class GST from Taenia solium are reported, revealing structural flexibility and glutathione interactions.

## Key findings

- The apo-form structures of rTs24GST show typical GST fold with flexible regions near the G-site.
- Glutathione stabilizes the enzyme and reduces conformational fluctuations according to molecular dynamics simulations.
- Structural flexibility suggests evolutionary adaptation for interacting with diverse substrates.

## Abstract

Neglected tropical diseases pose a significant threat to global health, especially in low- and middle-income countries where treatment options are inadequate and transmission risk factors persist. One example is neurocysticercosis caused by Taenia solium. Sigma class glutathione transferases (Sigma GSTs) are key regulators of Th1 inflammatory responses, making them promising targets for development of therapies and vaccines. This study presents the first report on the crystallographic structures of recombinant 24-kDa sigma class GST from T. solium (rTs24GST), which were determined at resolutions of 1.30 and 1.75 Å. The apo-form structures show the typical GST fold with distinct N- and C-terminal domains and highlight regions of notable flexibility near the G-site. Molecular dynamics simulations show that the presence of glutathione stabilizes the enzyme and reduces conformational fluctuations. Comparative analysis with other GSTs revealed conserved flexible regions that correlate with glutathione binding. These structural insights into rTs24GST can be associated with evolutionary adaptations for interacting with diverse substrates and could open new avenues for developing inhibitors and therapeutic strategies against neurocysticercosis.

This study focuses on the structural and functional analysis of a recombinant sigma class 24-kDa GST from T. solium (rTs24GST), the worm responsible for human neurocysticercosis, an important neglected tropical disease. Using advanced techniques such as crystallography and molecular dynamics simulations, we determined the high-resolution structure of a rTs24GST, providing new insights into how this enzyme interacts with glutathione, an essential molecule for cellular protection and regulation of immune response. Our findings reveal that the presence of glutathione significantly stabilizes the enzyme, reducing its fluctuations. This suggests that the enzyme’s activity may be influenced by its interaction with glutathione, offering potential avenues for developing new inhibitors or therapeutic strategies targeting neurocysticercosis. Although rTs24GST shows lower activity than other GSTs, its structural flexibility analysis suggests that it may have evolved to interact with a broader range of substrates. This evolutionary adaptation could indicate that this enzyme performs additional functions beyond traditional detoxification processes. These structural insights could prove valuable for the development of new treatments for neurocysticercosis, benefiting affected populations worldwide.