Engineering High Catalytic Efficiency of the Steroid Isomerase Activity of Human Glutathione S-transferase P1-1

Abstract

Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that catalyze the formation of conjugates between reduced glutathione (GSH) and a variety of carcinogenic, mutagenic, toxic and pharmacologically active compounds. 1,2 GSTs have also been shown to participate in other biological process. Certain GSTs can detoxify lipid and DNA hydroperoxide by their intrinsic peroxidase activity, while others can catalyze the isomerization of certain steroids. Mammalian cytosolic GSTs, which exist as homo- or heterodimers, are grouped into at least seven distinct classes alpha, mu, pi, sigma, theta, sigma, kappa and zeta - according to their physical, chemical, immunological and structural properties. 1,3,4 Human pi-class hGST P1-1 contains eight arginine residues. Among them, Arg13 is the only residue conserved in all the known Pi class GSTs and in most of the Alpha class GSTs. The highly conserved residues are expected to be important to the enzyme's structure and function. hGST P1-1 is particularly interesting as it can be used as a reliable preneoplastic or neoplastic marker because it is expressed at raised levels by a number of human tumors. 5,6 It has also