Structural insights into sigma class glutathione transferase from Taenia solium: Analysis and functional implications
Por:
Miranda-Blancas R., García-Gutiérrez P., Sánchez-Juárez C., Cardona-Echavarría M.C., Flores-López R., Zubillaga R.A., Rodríguez-Lima O., Sánchez-Pérez L.C., Rudiño-Piñera E., Landa A.
Publicada:
1 ene 2025
Resumen:
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. Copyright: © 2025 Miranda-Blancas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Filiaciones:
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de Mexico, Mexico
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, Mexico
Departamento de Medicina Molecular y Bioprocesos, Laboratorio de Bioquímica Estructural, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México, Edificio D, Circuito de Posgrados, 1° PisoCiudad Universitaria, Ciudad de México, Mexico
|