title: Crystal structure of herbicide-detoxifying maize glutathione S-transferase-I in complex with lactoylglutathione: evidence for an induced-fit mechanism.
abstract: Glutathione S-transferases (GSTs) -I and -III are involved in herbicide metabolism in maize and have been intensively studied. Starting with plant tissue from Zea mays var. mutin recombinant GST-I was prepared by heterologous expression in Escherichia coli. The enzyme was crystallized in the presence of lactoylglutathione, a ligand formerly never observed in a GST structure and known as an intermediate of the pharmacologically relevant glyoxalase system. The crystal structure of GST-I has been determined at 2.5 A resolution and exhibits the GST-typical dimer of two identical subunits, each consisting of 214 residues. Compared with other plant GSTs the three-dimensional structure of GST-I primarily shows structural differences in the hydrophobic substrate binding site, the linker segment and the C-terminal region. Furthermore, a comparison of the ligand-bound GST-I structure with the apo structure of GST-III indicates the movement of a ten-residue loop upon binding of the ligand to the active site. This is the first structure-based evidence for an induced fit mechanism of glutathione S-transferases, which has previously been postulated for class pi enzymes. Together with GST-III, GST-I may explain herbicide resistance and selectivity in maize as well as in other agronomic relevant crops.
authors.affiliation: Max-Planck-Institut für Biochemie, Am Klopferspitz, Martinsried, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Neuefeind
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: H
authors.initials: H
authors.lastname: Dasenbrock
authors.forename: L
authors.initials: L
authors.lastname: Prade
authors.forename: B
authors.initials: B
authors.lastname: Bieseler
mesh_terms: D017360:Arabidopsis / Q000201:enzymology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism*; D006540:Herbicides / Q000378:metabolism; D008658:Inactivation, Metabolic; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D003313:Zea mays / Q000201:enzymology*
chemical_list: D006540:Herbicides; D005982:Glutathione Transferase; D005978:Glutathione; C013585:S-lactoylglutathione