Glycation is a spontaneous protein modification associated with aging and disease. The Parkinson-associated protein DJ-1 is a multi-purpose enzyme that has been reported to have deglycase activity that can reverse glycation in proteins, making it an attractive therapeutic target. In this work, we demonstrate that DJ-1 is not a deglycase and instead protects against glycation by detoxifying the potent glycating agent methylglyoxal. In vitro assays using mass spectrometry and western blot reveal that DJ-1 is unable to deglycate both proteins and peptides and can only reduce levels of glycation when concurrently added to a glycation reaction. Our studies confirm that DJ-1 has glyoxalase activity that allows it to convert methylglyoxal to lactate and show that by pretreating methylglyoxal with DJ-1 we obtain a comparable decrease in glycation. We conclude that DJ-1 is a glycation antagonist by purifying MGO but is not a genuine deglycase.

DJ-1 is a glycation antagonist, not an AGE eraser

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.