Insights into ligand binding to a glutathione S-transferase from mango: Structure, thermodynamics and kinetics

Abstract

We studied a mango glutathione S-transferase (GST) (Mangifera indica) bound to glutathione (GSH) and S-hexyl glutathione (GSX). This GST Tau class (MiGSTU) had a molecular mass of 25.5 kDa. MiGSTU Michaelis-Menten kinetic constants were determined for their substrates obtaining a K_m, V_max and k_cat for CDNB of 0.792 mM, 80.58 mM min^-1 and 68.49 s^-1 respectively and 0.693 mM, 105.32 mM min^-1 and 89.57 s^-1, for reduced GSH respectively. MiGSTU had a micromolar affinity towards GSH (5.2 μM) or GSX (7.8 μM). The crystal structure of the MiGSTU in apo or bound to GSH or GSX generated a model that explains the thermodynamic signatures of binding and showed the importance of enthalpic-entropic compensation in ligand binding to Tau-class GST enzymes.

Keywords: Crystal structure; Detoxification; Glutathione; Glutathione S-transferase; Isothermal titration calorimetry; Mangifera indica; Mango; S-hexyl glutathione; Tau class.