HUMAN GLUTATHIONE S-TRANSFERASE A1-1 BINDING WITH NATURALLY OCCURRING LIGANDS: ASSESSMENT BY DOCKING SIMULATIONSAbstract
Glutathione S-transferases are phase-II enzymes associated with detoxification and resistance to drugs and xenobiotics. The majority of human tumors and human tumor cell lines express significant amounts of alpha class Glutathione S-Transferase A1-1. Present study aimed to examine hGSTA1-1 interaction with some naturally occurring ligands using docking simulations. Docking simulation using Glutathione S-transferases A1-1 monomer without Glutathione conjugate was receptor against Glutathione, Ellagic acid, Lycopene, α-Tocopherol acetate, Quercetin, Ethacrynic acid, Caffeic acid, Porphyrin, Ferulic acid, Curcumin, Dithiothreitol, Cinnamic acid, Iodoacetamide, α-Tocopherol, Beta-mercaptoethanol showed that the majority ligands tested bound at sites bordering the enzyme subunit-subunit interface. Docking results showed that all the selected ligands docked satisfactorily to the hGSTA1-1 enzyme. Lycopene has a strong binding affinity (Binding energy:-10.68 kcal/mol; docking energy: -15.96 kcal/mol) with hGSTA1-1 amongst selected ligands and predicted as a strong inhibitor against hGSTA1-1. In contrast, investigations using hGSTA1-1 monomer revealed there are additional sites for Ethacrynic acid, Betamercaptoethanol and Glutathione binding rather than H-site as expected from X-ray crystallographic data. In conclusion, the docking simulations suggest that the enzyme subunit interface may be important for hGSTA1-1 interactions with ligands. These findings may provide valuable insights for further research to identify naturally occurring therapeutic agents.
R. Srivastava *, S. Akthar, R. Sharma and S. Mishra
Department of Biotechnology, IFTM University, Moradabad, Uttar Pradesh, India.
14 March 2014
08 May 2014
28 June 2014
01 July 2014