Glutathione Transferases

The glutathione (GSH) transferases remain one of the most thoroughly understood group of detoxication enzymes. The structures and regulatory aspects of the genes encoding the canonical enzymes are as well understood as any. Their involvement in the biotransformation of many endogenous and xenobiotic electrophiles is well understood at the enzymological level. High-resolution three-dimensional structures of numerous isoenzymes are known from which the molecular details of catalysis can be inferred and tested with enzymological techniques. The structures also provide the basis for the design of isoenzyme-specific inhibitors and even prodrugs that may ultimately be useful in a clinical setting. The GSH transferases have provided a physical and theoretical scaffold on which to explore techniques for the design or identification of enzymes with novel substrate specificities and increased activity. Recent studies have revealed novel roles for the GSH transferases in the metabolism of endogenous substrates and in the regulation of cell signaling pathways. Further understanding of the biological effects of their involvement in biotransformations will allow the full weight of the structural and mechanistic insights to be brought to bear on designing clinically and environmentally useful compounds.