A novel selenium-containing glutathione transferase zeta1-1, the activity of which surpasses the level of some native glutathione peroxidases

Glutathione peroxidase (GPX) is a critical antioxidant selenoenzyme in organisms that protects cells against oxidative damage by catalyzing the reduction of hydroperoxides by glutathione (GSH). Thus, some GPX mimics have been generated because of their potential therapeutic value. The generation of...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2008, Vol.40 (10), p.2090-2097
Main Authors: Zheng, Keyan, Board, Philip G., Fei, Xiaofang, Sun, Ye, Lv, Shaowu, Yan, Ganglin, Liu, Junqiu, Shen, Jiacong, Luo, Guimin
Format: Article
Language:English
Subjects:
Catalysis - drug effects
Chemical mutation
Enzyme mimics
Glutathione peroxidase
Glutathione Peroxidase - metabolism
Glutathione Transferase - metabolism
Human glutathione transferase zeta1-1
Humans
Kinetics
Selenium - metabolism
Selenium-containing human glutathione transferase zeta1-1
Serine - metabolism
Spectrum Analysis
Tosyl Compounds - pharmacology
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Summary:Glutathione peroxidase (GPX) is a critical antioxidant selenoenzyme in organisms that protects cells against oxidative damage by catalyzing the reduction of hydroperoxides by glutathione (GSH). Thus, some GPX mimics have been generated because of their potential therapeutic value. The generation of a semisynthetic selenoenzyme with peroxidase activity, which matches the catalytic efficiencies of naturally evolved GPX, has been a great challenge. Previously, we semisynthesized a GPX mimetic with high catalytic efficiency using a rat theta class glutathione transferase (rGST T2-2) as a scaffold, in which the highly specific GSH-binding site is adjacent to an active site serine residue that can be chemically modified to selenocysteine (Sec). In this study, we have taken advantage of a new scaffold, hGSTZ1-1, in which there are two serine residues in the active site, to achieve both high thiol selectivity and highly catalytic efficiency. The GPX activity of Se-hGSTZ1-1 is about 1.5 times that of rabbit liver GPX, indicating that the selenium content at the active site plays an important role in enhancement of catalytic performance. Kinetic studies revealed that the catalytic mechanism of Se-hGSTZ1-1 belong in a ping–pong mechanism similar to that of the natural GPX.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2008.02.006