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

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dc.contributor.author Akhmadi, Aizhan
dc.contributor.author Yeskendir, Adilkhan
dc.contributor.author Dey, Nelly
dc.contributor.author Mussakhmetov, Arman
dc.contributor.author Shatkenova, Zariat
dc.contributor.author Kulyyassov, Arman
dc.contributor.author Andreeva, Anna
dc.contributor.author Utepbergenov, Darkhan
dc.contributor.author Shatkenova, Zariat
dc.contributor.author Kulyyassov, Arman
dc.contributor.author Andreeva, Anna
dc.contributor.author Utepbergenov, Darkhan
dc.date.accessioned 2024-09-19T10:20:03Z
dc.date.available 2024-09-19T10:20:03Z
dc.date.issued 2023
dc.identifier.issn 20411723
dc.identifier.other doi.org/10.1038/s41467-024-46391-9
dc.identifier.uri http://rep.enu.kz/handle/enu/16682
dc.description.abstract 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. This acylation is indirect and thought to proceed via the formation of an unstable intermediate, presumably a cyclic 3-phosphoglyceric anhydride (cPGA). Several lines of evidence indicate that DJ-1 destroys cPGA, however this enzymatic activity has not been directly demonstrated. Here, we report simple and effective procedures for synthesis and quantitation of cPGA and present a comprehensive characterization of this highly reactive acylating electrophile. We demonstrate that DJ-1 is an efficient cPGA hydrolase with kcat/Km = 5.9 × 106 M−1 s−1 . Experiments with DJ-1-null cells reveal that DJ-1 protects against accumulation of 3-phosphoglyceroyl-lysine residues in proteins. Our results establish a definitive cytoprotective function for DJ-1 that uses catalytic hydrolysis of cPGA to mitigate the damage from this glycolytic byproduct. ru
dc.language.iso en ru
dc.publisher Nature Communications ru
dc.relation.ispartofseries Том 15, Выпуск 1;
dc.title DJ-1 protects proteins from acylation by catalyzing the hydrolysis of highly reactive cyclic 3-phosphoglyceric anhydride ru
dc.type Article ru


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