Human liver glutathione S-transferase ψ. Chemical characterization and secondary-structure comparison with other mammalian glutathione S-transferases

The isolation and chemical characterization of the anionic human liver glutathione S-transferase (GST) ψ (pI 5.5) are described and compared with other GST isoenzymes reported for rat and human. Amino acid compositional analysis, substrate specificity and isoelectric focusing indicated that GST ψ is a unique isoenzyme form of GST. Strikingly, however, amino acid sequence analysis of the N-terminal region indicated that GST ψ was identical with GST μ in the first 23 amino acid residues reported. It is likely that these two enzyme forms are at least partially structurally related. In order to investigate further the genetic relationship of GST ψ to other reported GST isoenzymes, secondary-structure analysis was performed. Despite substantial differences in the N-terminal-region amino acid sequences of some of the GST isoenzymes, the secondary structure of all the isoenzymes is highly conserved at their N-termini. The general uniformity of the secondary structure of this enzyme class at their N-termini strongly indicated that the observed diversity of these isoenzymes probably occurred as a result of a mechanism of gene duplication followed by divergence rather than a mechanism of convergent evolution.