Structural classes of glutathione transferase: distinctions between isoenzymes and enzymes.

The amino acid sequences of the five cytosolic rat glutathione transferases 1-1, 2-2, 3-3, 4-4, and 7-7 of three different classes have been compared. Alignments demonstrate 68%-78% positional identity between isoenzymes within the same class, and 29%-32% between the enzymes of different classes. Of the 209-221 residues in the structures, those strictly conserved are limited to 24, over half of which are charged residues and Leu, while few are Gly and Pro that in related proteins otherwise are often maintained because of space restrictions and conserved conformations. In spite of the limited sequence homologies, hydropathy profiles and predictions of secondary structures emphasize the relationship between the three enzyme classes. The predictions indicate alternating alpha-helices and beta-strands, a chain fold typical for alpha/beta protein structures. Glutathione transferases within a class are highly similar and may be regarded as true isoenzymes, while transferases of different classes appear to occupy an intermediate stage between isoenzymes and discrete enzymes.