Describing the interaction between Wuchereria bancrofti glutathione transferase and Bromosulphophthalein from an empirical and theoretical perspective

Wuchereria bancrofti glutathione transferase (WbGST) is a therapeutic target in the parasitic worms that cause lymphatic filariasis. We described the molecular and structural basis of WbGST inhibition by Bromosulphophthalein (BSP) and compared it with human Mu (hGSTMu) and Pi (hGSTPi) class GSTs. BSP inhibited WbGST activity with an IC₅₀ of 5 μM, 13.5 μM for the hGSTMu, and 110 μM for hGSTPi. Fluorescence spectroscopy showed that BSP altered polarity of intrinsic tryptophan residue environment and decreased the interaction between the enzymes and 8-Anilino-1-naphthalenesulphonate (ANS), a known GST H-site ligand. A computational modelling study to validate our empirical data showed that BSP binding at H-site and dimer interface of WbGST elicited diverse structural dynamics. Serial and comparative critical binding pocket studies suggest that the preferred WbGST binding pocket for interaction and stabilisation of BSP appears to be at the dimer interface. Interacting and directing energies seem clustered at the dimer interface of the WbGST, thus blocking off-targeting of the human GSTs. Structural dynamics and stability investigations suggest that WbGST experienced a more potent inhibitory outcome than the two human GSTs, corresponding to our in vitro empirical studies. These findings will provide an opportunity to design new chemotherapeutics for treating filariasis.