Protein Repair from Glycation by Glyoxals by the DJ-1 Family Maillard Deglycases

Abstract

DJ-1 and its prokaryotic homologs, Hsp31, YhbO and YajL from Escherichia coli and PfpI from Pyrococcus furiosus, repair proteins from glycation by glyoxals (R-CO-CHO), which constitute their major glycating agents. Glycation is a non-enzymatic covalent reaction discovered by Louis Camille Maillard in 1912, between reactive carbonyls (reducing sugars and glyoxals) and amino acids (cysteine, arginine and lysine), which inactivates proteins. By degrading Maillard adducts formed between carbonyls and thiols or amino groups, the DJ-1 family Maillard deglycases prevent the formation of the so-called advanced glycation end products (AGEs) that arise from Maillard adducts after dehydrations, oxidations and rearrangements. Since glycation is involved in ageing, cancer, atherosclerosis and cataracts, as well as post-diabetic, neurovegetatives and renal and autoimmune diseases, the DJ-1 deglycases are likely to play an important role in preventing these diseases. These deglycases, especially those from thermophilic organisms, may also be used to prevent the formation of dietary AGEs during food processing, sterilization and storage. They also prevent acrylamide formation in food, likely by degrading the asparagine/glyoxal Maillard adducts responsible for its formation. Since Maillard adducts are the substrates of the DJ-1 family deglycases, we propose renaming them Maillard deglycases.

A Novel Pyrazolopyrimidine Ligand of Human PGK1 and Stress Sensor DJ1 Modulates the Shelterin Complex and Telomere Length Regulation

“…Recently, novel cellular protection roles for DJ1 as a glyoxalase and deglycating enzyme for both proteins and nucleic acids have been reported [35], [36], [37]. Methylglyoxal, one of the principal cellular glycating species is produced from glycolytic intermediates dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, which are generated by the aldolase glycolysis reaction upstream of PGK1 [35] and were increased by CRT0063465 (Figure S3 and S4, and table S1 in Supplementary File 2).…”

“…The role of the PGK1/DJ1 complex identified here remains to be determined, though previous studies have suggested functional coupling between DJ1 and glycolysis. Interaction with PGK1 would localize DJ1 close to sites of methylglyoxal production, where its glyoxalase and deglycating activities would be most effective [35], [36], [37]. At the same time, it is plausible that this activity acts as a sensor of upstream glycolytic intermediate concentrations facilitating feedback regulation of glycolytic rate.…”

DJ-1 in Parkinson’s Disease: Clinical Insights and Therapeutic Perspectives

“…Strikingly, despite concerted efforts by the scientific community, it is still unclear how DJ-1 contributes to PD pathogenesis. Indeed, a plethora of different functions have been ascribed to DJ-1 (for detailed reviews see [25,26,27]), which complicates our understanding of how DJ-1 mutations specifically cause PD. In order to shed some light on DJ-1 biology, here we underline what we do know about DJ-1:DJ-1 is highly expressed in cells with high energy demands, hence cells with higher levels of reactive oxygen species.…”

The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction

“…This class of enzymes would also prevent acrylamide formation in food, likely by degrading the asparagine/glyoxal Maillard adducts responsible for its formation. [ 103 ]…”