CRYSTAL STRUCTURE OF ISOZYME 4-4 & MOLECULAR MODELING OF ISOZYME 3-4 OF CLASS MU GLUTATHIONE S-TRANSFERASES FROM RAT LIVER. Gaoyi Xiao,¹ Xinhua Ji,^1,2 Richard Armstrong,³ and Gary L. Gilliland^{1, 1}Center for Advanced Research in Biotechnology of the University of Maryland Biotechnology Institute and the National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, MD 20850. ²NCI-FCRDC, P.O. Box B, Frederick, MD 21702. ³Department of Biochemistry and the Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232

Glutathione S-transferases (GST) are a family of phase-II detoxification enzymes that may also play a role as transport proteins. To date, five different gene classes, alpha, mu, pi, theta and sigma, of this dimeric enzyme have been identified. Several subunit types have been found for the different gene classes in many different organisms. Heterodimers composed of different subunits of the same gene class are commonly isolated. Interclass heterodimers, however, have not been observed [1]. We report here the crystal structure of the 50 kDa 4-4 isozyme of the rat liver mu GST. The three-dimensional structure was determined at 3.5 Å resolution by the molecular replacement method using the 3-3 isozyme of the rat liver mu GST [2]. This represents the first example of the structure of a second GST subunit type from the same gene class. Details of the 4-4 mu GST structure, results of an analysis of the interface interactions of the two homodimeric structures, and results of molecular modeling of the heterodimeric 3-4 mu GST isozyme to learn what features at the dimer interface allow heterodimer formation will be presented.

[1] Armstrong, R., (1994) Advances in Enzymology & Related Areas in Molecular Biology 69, 1-44.

[2] Ji, X., Zhang, P., Armstrong, R. N. and Gilliland, G. L. (1994) Biochemistry 31, 10169-10184.