cPGA hydrolase assay of DJ-1 in crude cell lysates: Implications for sensing of oxidative stress.

Cyclic 3-phosphosphoglyceric anhydride (cPGA), a side product of glycolysis, acylates cellular amines and thiols to form amides and thioesters, respectively. Since these acylation reactions are harmful, organisms rely on a protein, known as DJ-1 in humans, to inactivate cPGA. Inactivation of cPGA likely plays a significant role in cytoprotection by DJ-1, but further progress in this direction is hampered by the lack of quantitative assays to measure the cPGA hydrolase activity of DJ-1 in biological samples.

DJ-1 protects proteins from acylation by catalyzing the hydrolysis of highly reactive cyclic 3-phosphoglyceric anhydride.

Mutations in the human PARK7 gene that encodes protein DJ-1 lead to familial Parkinsonism due to loss of dopaminergic neurons. However, the molecular function of DJ-1 underpinning its cytoprotective effects are unclear. Recently, DJ-1 has been shown to prevent acylation of amino groups of proteins and metabolites by 1,3-bisphosphoglycerate.