CRYSTAL-STRUCTURE OF HERBICIDE-DETOXIFYING MAIZE GLUTATHIONE S-TRANSFERASE-I IN COMPLEX WITH LACTOYLGLUTATHIONE - EVIDENCE FOR AN INDUCED-FIT MECHANISM

Glutathione S-transferases (GSTs) -I and -III are involved in herbicid e metabolism in maize and have been intensively studied. Starting with plant tissue from Zen mays var. mutin recombinant GST-I was prepared by heterologous expression in Escherichia coli. The enzyme was crystal lized in the presence of lactoylglutathione, a ligand formerly never o bserved in a GST structure and known as an intermediate of the pharmac ologically relevant glyoxalase system. The crystal structure of GST-I has been determined at 2.5 Angstrom resolution and exhibits the GSP-ty pical dimer of two identical subunits, each consisting of 214, residue s. Compared with other plant GSTs the three-dimensional structure of G ST-I primarily shows structural differences in the hydrophobic substra te binding site, the linker segment and the C-terminal region. Further more, a comparison of the ligand-bound GST-I structure with the apo st ructure of GST-III indicates the movement of a ten-residue loop upon b inding of the ligand to the active site. This is the first structure-b ased evidence for an induced Lit mechanism of glutathione S-transferas es, which has previousely been postulated for class pi enzymes. Togeth er with GST-III, GST-I may explain herbicide resistance and selectivit y in maize as well as in other agronomic relevant crops. (C) 1997 Acad emic Press Limited.