Glutathione transferase-P1-1 binding with naturally occurring ligands: assessment by docking simulations


Glutathione transferase-P1-1 (hGSTP1-1), which is associated with acquired drug resistance in some tumour cells, requires two identical subunits for full activity. Naturally occurring inhibitors for GSTP1-1 quaternary structure could be interesting therapeutic agents. The aim of this study was to investigate potential binding sites for hGSTP1-1 interaction with ligands many of which occur naturally. Simulations were performed with commercial docking software and with GST monomer or dimer as template. Docking results using hGSTP1-1 dimer showed one binding site for most of the ligands tested. Lycopene, glutathione, ellagic acid, ethacrynic acid, quercetin, caffeic acid, ferulic acid, porphyrin, curcumin, cinnamic acid, and also α-tocopherol bound at the enzyme dimer subunit-subunit interface. In contrast, investigations using hGSTP1-1 monomer revealed three additional sites for ligand binding. In conclusion, the docking simulations suggest that the enzyme subunit interface may be important for hGSTP1-1 interactions with ligands. These findings may provide valuable insights for further research to identify naturally occurring therapeutic agents.

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Das, A. , Chalil, S. , Nigam, P. , Magee, P. , Janneh, O. and Owusu-Apenten, R. (2011) Glutathione transferase-P1-1 binding with naturally occurring ligands: assessment by docking simulations. Journal of Biophysical Chemistry, 2, 401-407. doi: 10.4236/jbpc.2011.24046.

Conflicts of Interest

The authors declare no conflicts of interest.


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