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  • Structure and function of the proapoptotic oxidoreductase PIG3

    images29The p53 tumor suppressor gene regulates the expression of p53-induced genes (PIG: p53 induced genes) that initiate apoptosis. The PIG3 or TP53I3 is the only member of the superfamily of dehydrogenases / reductases medium chain induced p53 proapoptotic be used as a marker. Although it is well known PIG3 participation in the apoptotic pathway or protein or its mechanism of action have been well characterized.

    This paper has analyzed the enzymatic function PIG3 finding that has NADPH-dependent reductase activity against ortoquinonas. However, this reductase activity is much lower than that of the ζ-crystalline (quinone reductase). Furthermore, these investigators have described the crystal structure of the PIG3, which has enabled the identification of the cofactor binding sites, the substrates and possesses conserved residues from bacteria to humans. Moreover, it has been suggested that Tyr-59 of the ζ-crystalline (Tyr-51 in PIG3) is involved in catalyzing the reduction of quinone.

    Kinetic studies with mutant Tyr / Phe and Tyr / Ala in both enzymes have shown that Tyr is not in the catalytic center, but participates in substrate binding and is consistent with a mechanism based on the effects of proximity. Moreover, the contribution of PIG3 in apoptosis may be through the generation of oxidative stress. PIG3 overexpression systems in vitro and in vivo accumulates reactive oxygen species (ROS). Similarly, an inactive mutant of PIG3 (S151V) did not produce ROS in cells, indicating that enzymatically active protein is required for this function. With this the authors conclude that PIG3 action is via oxidative stress resulting from its enzymatic activity.

    Published on November 3, 2012 · Filed under: Bioscience, News; Tagged as: , ,
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