Glutathione transferase: A first-principles study of the active site

We present a first-principles study of the interaction of glutathione (GSH) with the enzyme glutathione transferase (GST) and its Y6F mutant. By compa ring a reduced model (5-19 atoms) of the interacting species with a larger model (127-131 atoms) including five amino acids of GST, we show that the p rotein environment effects must be taken into account to properly model the active site. We find that, in the case of the Tyr --> Phe mutant, the expe rimental data on pK are reproduced, assuming that a water molecule interact s with the thiol group of GSH. Our results help to elucidate the role that Tyr and water may play as H-bond donors to the thiol group in the enzymatic reaction of GST.