The glutathione S-transferases are a family of enzymes that catalyze the addition of the tripeptide glutathione to endogenous and xenobiotice substrates which have electrophilic functional groups. They play an important role in the detoxication and metabolism of many xenobiotic and endobiotic compounds. The glutathione adducts produced have increased solubility in water and are subsequently enzymatically degraded to mercapturates and excreted.

About the structure:

Glutathione S-transferases are dimeric with subunits of 25 kDa molecular weight. The occurance of multiple genes for the subunits results in enzymes that are homo- or heterodimers.

This work in done in collaboration with Richard Armstrong's group at Vanderbilt University Medical Center.

Publications:

"Contribution of tyrosine 6 to the catalytic mechanism of isoenzyme 3-3 of glutathione S-transferase", Liu, S., Zhang, P., Ji, X., Jownson, W.W., Gilliland, G.L., and Armstrong, R. J. Biol. Chem., 267, 4296-4299 (1992).

"The Three-Dimensional Structure of a Glutathione S-Transferase from the mu Gene Class: Structural Analysis of the Binary Complex of Isozyme 3-3 and Glutathione at 2.2 � Resolution", Ji, X., Zhang, P., Armstrong, R.N., and Gilliland, G.L., Biochemistry, 31, 10169-10184 (1992).

"Modular Mutagenesis of Exons 1,2 and 8 of a Glutathione S-Transferase from the mu Class. Mechanistic and Structural Consequences for Chimeras of Iosenzyme 3-3", Zhang, P., Liu, S., Ji, X., Gilliland, G.L., and Armstrong, R.N., Biochemistry, 31, 10185-10192 (1992).

"Structure Determination and Refinement of Human Alpha Class Glutathione Transferase A1-1", Sinning, I., Kleywegt, G.J., Cowan, S.W., Reinemer, P., Din, H.W., Huber, R., Gilliland, G.L., Armstrong, R.N., Ji, X., Board, P.G., Olin, B., Mannervick, B., and Jones, A., J. Mol. Biol., 232, 192-212 (1993).

"Tyrosine 115 Participates Both in Chemical and Physical Steps of the Catalytic Mechanism of Isozyme 3-3 of Glutathione S-Transferase", Johnson, W.W., Liu, S., Ji, X., Gilliland, G.L., and Armstrong, R.N., J. Biol. Chem., 268, 11508-11511 (1993).

"Crystallographic and Mechanistic Studies of Class MU Glutathione S-Transferases", Armstrong, R.N., Gilliland, G.L., Ji, X., Johnson, W.W., and Liu, S, in Proceedings of the International Meeting on Structure and Function of Glutathione Transferases (Tew, K.D., Pickett, C.B., Mantle, T.J., Mannervik, B., and Hayes, J.D., eds.), CRC Press, Boca Raton, pp. 87-99 (1993).

"Second-Sphere Electrostatic Effects in the Active Site of Glutathione S-Transferase. Observations of an On-Face Hydrogen Bond Between the Side-Chain of Threonine 13 and the -Cloud of Tyrosine 6 and Its Influence on Catalysis", Liu, S., Ji, X., Gilliland, G.L., Stevens, W.J. and Armstrong, R.N., JACS, 115, 7910-7911 (1993).

"Snapshots Along the Reaction Coordinate of an S_NAr Reaction Catalyzed by Glutathione Transferase", Ji, X., Armstrong, R.N., and Gilliland, G.L., Biochemistry, 32, 12949-12954 (1993).

"Structure and Function of the Xenobiotic Substrate Binding Site of a Glutathione S-Transferase as Revealed by X-Ray Crystallographic Analysis of Product Complexes with the Diastereomers of 9-(S-Glutathionyl)-10-Hydroxy-9,10-Dihydrophenanthrene", Ji, X., Johnson, W. W., Sesay, M.A., Dickert, L., Prasad, S.M., Ammon, H.L., Armstrong, R.N., and Gilliland, G.L., : Biochemistry, 33, 1043-1052 (1994).

"The Three-Dimensional Structure of Glutathione S-Transferase of Schistosoma japonicum Fused with a Conserved Neutralizing Epitope on gp41 of Human Immunodeficiency Virus Type I", Lim, K., Ho, J.X., Keeling, K., Gilliland, G.L., Ji, X., Ruker, F., and Carter, D.C., Protein Science, 3, 2233-2244 (1994).

"Three-Dimensional Structure, Catalytic Properties and Evolution of a Sigma Class Glutathione Transferase from Squid, A Progenitor of the Lens S-Crystallins of Cephalopods", Ji, X., von Roxenvinge, E.C., Johnson, W.W., Tomarev, S.I., Piatigorsky, J., Armstrong, R.N., and Gilliland, G.L., Biochemistry 34, 5317-5328 (1995).

"Structure, Mechanism and Evolution of Class Mu and Sigma Glutathione Transferases", Armstrong, R.N., Chen, J., Johnson, W.W., Parsons, J., Ji, X., Gilliland, G.L., in Glutathione S-Transferases: Structure, Function, and Clinical Implications, (eds., Vermeulen, N.P.E., Mulder, G.J., Niuwenhuyse, H., Peters, W.H.M., and van Bladeren, P.J.)Taylor and Frances, Ltd., London 13-22 (1995).

"First-Sphere and Second-Sphere Electrostatic Effects in the Active Site of a Class Mu Glutathione Transferase", Xiao, G., Liu, S., Ji, X., Johnson, W.W., Chen, J., Parsons, J.F., Stevens, W.W., Gilliland, G.L. and Armstrong, R.N., Biochemistry 35, 4753-4765 (1996).

"Location of a Potential Transport Binding Site in a Sigma Class Glutathione Transferase by X-ray Crystallography", Ji, X., von Rosenvinge, E.C., Jonhson, W.W., Armstrong, R.N., and Gilliland, G.L., Proc. Natl. Acad. Sci. U.S.A. 93, 8208-8213 (1996).

"Structure and Function of the Xenobiotic Substrate Binding Site and Location of a Potential Non-Substrate Binding Site in a Pi Class Glutathione S-Transferase", Ji, X., Tordova, M., O'Donnell, R., Parsons, J.F., Hayden, Gilliland, G.L., and Zimniak, P., Biochemistry, 36, 9690-9702 (1997).

"Crystal Structure of Tetradeca-(3-Fluorotyrosyl)-Glutathione Transferase", Xiao, G., Parsons, J.F., Armstrong, R.N., and Gilliland, G.L., JACS 119, 9325-9326 (1997).

"Enzymes Harboring Unnatural Amino Acids: Mechanistic and Structural Analysis of the Enhanced Catalytic Activity of a Glutathione Transferase Containing 5-Fluorotryptophan", Parsons, J.F., Xiao, G., Gilliland, G.L., and Armstrong, R.N., Biochemistry 37, 6286-6294 (1998).

"Conformational Changes in the Crystal Structure of Rat Glutathione Transferase M1-1 with Global Substitution of 3-Fluorotyrosine for Tyrosine", Xiao, G., Parsons, J.F., Tesh, K., Armstrong, R.N., and Gilliland, G.L., J. Mol. Biol. 281, 323-339 (1998).

"Local protein dynamics and catalysis: detection of segmental motion associated with rate-limiting product release by a glutathione transferase", Codreanu, S.G., Ladner, J.E., Xiao, G., Stourman, N.V., Hachey, D.L., Gilliland, G.L., and Armstrong, R.N., Biochemistry 41, 15161-15172 (2002).