Evaluation of possible active site residues in GSTZ 1-1

Zeta class of glutathione transferases are responsible for several novel gl utathione-dependent reactions including the isomerization of maleylacetoace tate to fumarylacetoacetate and the biotransformation of a halo acids such as dichloroacetic acid (DCA). N-terminal domain Tyr, Ser, Arg and Cys resid ues have been implicated in catalysis in other GST classes. PI model struct ure for the N-terminal domain implicates Ser 14 as a significant active sit e residue and its mutation to Ala inactivates GSTZl-1 with DCA and chlorofl uroacetate. In contrast the mutations Tyr9Phe and Cys16Ala give rise to inc reased activity with DCA. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.