title: Insights into the catalytic mechanism of glutathione S-transferase: the lesson from Schistosoma haematobium.
abstract: Glutathione S-transferases (GSTs) are involved in detoxification of xenobiotic compounds and in the biosynthesis of important metabolites. All GSTs activate glutathione (GSH) to GS(-); in many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulfur of GSH. The high-resolution structure of GST from Schistosoma haematobium revealed that the catalytic Tyr occupies two alternative positions, one external, involving a pi-cation interaction with the conserved Arg21, and the other inside the GSH binding site. The interaction with Arg21 lowers the pK(a) of the catalytic Tyr10, as required for catalysis. Examination of several other GST structures revealed the presence of an external pocket that may accommodate the catalytic Tyr, and suggested that the change in conformation and acidic properties of the catalytic Tyr may be shared by other GSTs. Arginine and two other residues of the external pocket constitute a conserved structural motif, clearly identified by sequence comparison.
authors.affiliation: Istituto di Biologia e Patologia Molecolari del CNR, Department of Biochemical Sciences A. Rossi Fanelli, University of Rome La Sapienza, 00185 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelucci
authors.forename: Paola
authors.initials: P
authors.lastname: Baiocco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brunori
authors.forename: Louise
authors.initials: L
authors.lastname: Gourlay
authors.forename: Veronica
authors.initials: V
authors.lastname: Morea
authors.forename: Andrea
authors.initials: A
authors.lastname: Bellelli
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002384:Catalysis; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000737:chemistry*; D006860:Hydrogen Bonding; D011487:Protein Conformation; D012548:Schistosoma haematobium / Q000201:enzymology*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D014443:Tyrosine; D001120:Arginine; D005982:Glutathione Transferase