Evolutionary strategy for optimization of GSH binding and catalysis in Alpha, Pi, Mu and theta glutathione transferases

Abstract

The substrate binding mechanism and catalysis of the human glutathione transferase T2-2 have been studied and compared to those found in the more recently evolved Alpha, Mu and Pi class isoenzymes. The evolution strategy for the optimization of the binding process is based on the shift from a single-step to a multi-step interaction with the substrate. An evolutionary pressure in terms of flexibility of the protein and of proper orientation of the substrate may also explain the relevant differences of the catalytic properties found among the 'old' and 'young' isoenzymes. © 2001 Elsevier Science Ireland Ltd. All rights reserved.