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Article Dans Une Revue Biochemical Journal Année : 2009

Crystal structure of Glycine max glutathione transferase in complex with glutathione: investigation of the mechanism operating by the tau class glutathione transferases

Irene Axarli
  • Fonction : Auteur
Prathusha Dhavala
  • Fonction : Auteur
Anastassios C. Papageorgiou
  • Fonction : Auteur

Résumé

Cytosolic glutathione transferases (GSTs) are a multifunctional group of enzymes widely distributed in nature and involved in cellular detoxification processes. The three-dimensional structure of Glycine max GSTU4-4 (GmGSTU4-4) complexed with glutathione (GSH) was determined by the molecular replacement method at 2.7 Å resolution. The bound GSH is located in a region formed by the beginning of α-helices H1, H2 and H3 in the N-terminal domain of the enzyme. Significant differences in the GSH binding site (G-site) as compared to the structure determined in complex with S-(p-nitrobenzyl)-glutathione (Nb-GSH) were found. These differences were identified in the hydrogen-bonding and electrostatic interaction pattern and, consequently, GSH was found bound in two different conformations. In one subunit, the enzyme forms complex with the ionized form of GSH whereas in the other subunit with the non-ionized form; only the ionized form of GSH may form a productive and catalytically competent complex. Furthermore, a comparison of the GSH-bound structure with the Nb-GSH-bound structure shows a significant movement of the upper part of α-helix H4 and the C-terminal part. This indicates an intrasubunit modulation between the G-site and the electrophile binding site (H-site), suggesting that the enzyme recognizes the xenobiotic substrates by an induced-fit mechanism. The reorganization of Arg111 and Tyr107 upon xenobiotic substrate binding appears to govern the intrasubunit structural communication between G- and H-site and the binding of GSH. The structural observations were further verified by steady-state kinetic analysis and site-directed mutagenesis studies.

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hal-00479161 , version 1 (30-04-2010)

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Irene Axarli, Prathusha Dhavala, Anastassios C. Papageorgiou, Nikolaos E Labrou. Crystal structure of Glycine max glutathione transferase in complex with glutathione: investigation of the mechanism operating by the tau class glutathione transferases. Biochemical Journal, 2009, 422 (2), pp.247-256. ⟨10.1042/BJ20090224⟩. ⟨hal-00479161⟩

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