Effect of Glutathione on the Stability, Dynamics and Catalysis of Two Different Classes of Glutathione Transferases from Taenia solium
Por:
Sánchez Juárez C., Sánchez Pérez L.C., Zubillaga R.A., Flores-López R., Landa A., Jiménez L., Miranda-Blancas R., Rudiño-Piñera E., Cardona-Echavarría M.C., García-Gutiérrez P.
Publicada:
1 ene 2025
Resumen:
In this work we compare the effect of glutathione (GSH) on the stability and dynamics of two different classes of glutathione transferases from Taenia solium, Ts26GST (a/µ class) and Ts24GST (s class). The purpose was to explore why Ts24GST has low catalytic activity for the conjugation of glutathione (GSH) to hydrophobic substrates such as 1-chloro-2,4-dinitrobenzene (CDNB) compared to the very active Ts26GST but can instead use GSH to isomerize prostaglandin H2 to prostaglandin D2 by reducing its peroxide bond, a reaction described just for s class of cytosolic GSTs. Using our recently deposited structure of Ts24GST in the Protein Data Bank, and a previous model for Ts26GST, we determined by molecular dynamics simulations that the presence of GSH decreased the number of intramolecular hydrogen bonds of Ts24GST and increased its radius of gyration, while in Ts26GST the effect was to increase its number of intramolecular hydrogen bonds without significantly changing its radius of gyration. Consistent with this, the experimental thermal stability of Ts26GST increased markedly while that of Ts24GST decreased in the presence of GSH, as determined by intrinsic fluorescence measurements. On the other hand, the binding site for the hydrophobic substrate (H site) of Ts24GST is wider than the H site of Ts26GST, with a 31 % greater solvent-accessible surface area. © 2025, Sociedad Química de México.
Filiaciones:
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico
Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México, Mexico
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico
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