Evaluation of possible active site residues in GSTZ 1-1

Zeta class of glutathione transferases are responsible for several novel glutathione-dependent reactions including the isomerization of maleylacetoacetate to fumarylacetoacetate and the biotransformation of α halo acids such as dichloroacetic acid (DCA). N-terminal domain Tyr, Ser, Arg and Cys residues have been implicated in catalysis in other GST classes. A model structure for the N-terminal domain implicates Ser 14 as a significant active site residue and its mutation to Ala inactivates GSTZ1-1 with DCA and chlorofluroacetate. In contrast the mutations Tyr9Phe and Cys16Ala give rise to increased activity with DCA.