We present a first-principles study of the interaction of glutathione (GSH) with the enzyme glutathione transferase (GST) and its Y6F mutant. By comparing 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 protein 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 experimental data on pK are reproduced, assuming that a water molecule interacts 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.
Glutathione transferase: A first-principles study of the active site
De Angelis, F.;
2000
Abstract
We present a first-principles study of the interaction of glutathione (GSH) with the enzyme glutathione transferase (GST) and its Y6F mutant. By comparing 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 protein 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 experimental data on pK are reproduced, assuming that a water molecule interacts 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
