title: A semisynthetic glutathione peroxidase with high catalytic efficiency. Selenoglutathione transferase.
abstract: Glutathione peroxidase (GPX) protects cells against oxidative damage by catalyzing the reduction of hydroperoxides by glutathione (GSH). GPX therefore has potential therapeutic value as an antioxidant, but its pharmacological development has been limited because GPX uses a selenocysteine as its catalytic group and it is difficult to generate selenium-containing proteins with traditional recombinant DNA technology. Here, we show that naturally occurring proteins can be modified to generate GPX activity. The rat theta-class glutathione transferase T2-2 (rGST T2-2) presents an ideal scaffold for the design of a novel GPX catalyst because it already binds GSH and contains a serine close to the substrate binding site, which can be chemically modified to bind selenium. The modified Se-rGST T2-2 efficiently catalyzes the reduction of hydrogen peroxide, and the GPX activity surpasses the activities of some natural GPXs.
authors.affiliation: Key Laboratory for Supramolecular Structure and Materials of Ministry of Education, Jilin University, Changchun, China
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ren
authors.forename: Per
authors.initials: P
authors.lastname: Jemth
authors.forename: Philip G
authors.initials: PG
authors.lastname: Board
authors.forename: Guimin
authors.initials: G
authors.lastname: Luo
authors.forename: Bengt
authors.initials: B
authors.lastname: Mannervik
authors.forename: Junqiu
authors.initials: J
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Jiacong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000138:chemical synthesis / Q000378:metabolism*; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D007700:Kinetics; D010084:Oxidation-Reduction; D015202:Protein Engineering / Q000379:methods*; D012643:Selenium / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D000911:Antibodies, Monoclonal; D012694:Serine; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D012643:Selenium