Publications

• Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine and lysine residues.

  Richarme G., Mihoub M., Dairou J., Bui L.C., Leger T., Lamouri A.

  Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we ... >> More

  Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein. << Less

  J. Biol. Chem. 290:1885-1897(2015) [PubMed] [EuropePMC]

  This publication is cited by 11 other entries.

• The DJ-1 superfamily member Hsp31 repairs proteins from glycation by methylglyoxal and glyoxal.

  Mihoub M., Abdallah J., Gontero B., Dairou J., Richarme G.

  Hsp31 belongs to the PfpI/Hsp31/DJ-1 superfamily, and has been reported to display chaperone, peptidase and glutathione-independent glyoxalase activities. Here, we show that Hsp31 repairs glyoxal- and methylglyoxal-glycated amino acids and proteins and releases repaired proteins and lactate or gly ... >> More

  Hsp31 belongs to the PfpI/Hsp31/DJ-1 superfamily, and has been reported to display chaperone, peptidase and glutathione-independent glyoxalase activities. Here, we show that Hsp31 repairs glyoxal- and methylglyoxal-glycated amino acids and proteins and releases repaired proteins and lactate or glycolate, respectively. Hsp31 deglycates cysteine, arginine and lysine by acting on early glycation intermediates (hemithioacetals and aminocarbinols) and prevents the formation of Schiff bases and advanced glycation endproducts. Hsp31 repairs glycated serum albumin, glyceraldehyde-3-phosphate dehydrogenase, fructose biphosphate aldolase and aspartate aminotransferase. Moreover, we show that bacterial extracts from the hchA mutant display increased glycation levels and that the apparent glyoxalase activity of Hsp31 reflects its deglycase activity. Our results suggest that other Hsp31 members, previously characterized as glutathione-independent glyoxalases, likely function as protein deglycases. << Less

  Biochem. Biophys. Res. Commun. 463:1305-1310(2015) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Hsp31 of Escherichia coli K-12 is glyoxalase III.

  Subedi K.P., Choi D., Kim I., Min B., Park C.

  Hsp31 encoded by hchA is known as a heat-inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp-214, His-186 and Cys-185, its enzymatic function, besides weak amino-peptidase activity, is still unknown. We found that Hsp31 dis ... >> More

  Hsp31 encoded by hchA is known as a heat-inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp-214, His-186 and Cys-185, its enzymatic function, besides weak amino-peptidase activity, is still unknown. We found that Hsp31 displays glyoxalase activity that catalyses the conversion of methylglyoxal (MG) to d-lactate without an additional cofactor. The glyoxalase activity was completely abolished in the hchA-deficient strain, confirming the relationship between the hchA gene and its enzymatic activity in vivo. Hsp31 exhibits Michaelis-Menten kinetics for substrates MG with K(m) and k(cat) of 1.43±0.12 mM and 156.9±5.5 min⁻¹ respectively. The highest glyoxalase activity was found at 35-40 °C and pH of 6.0-8.0, and the activity was significantly inhibited by Cu²⁺, Fe³⁺ and Zn²⁺. Mutagenesis studies based on our evaluation of conserved catalytic residues revealed that the Cys-185 and Glu-77 were essential for catalysis, whereas His-186 was less crucial for enzymatic function, although it participates in the catalytic process. The stationary-phase Escherichia coli cells became more susceptible to MG when hchA was deleted, which was complemented by an expression of plasmid-encoded hchA. Furthermore, an accumulation of intracellular MG was observed in hchA-deficient strains. << Less

  Mol. Microbiol. 81:926-936(2011) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• The DJ-1 superfamily members YhbO and YajL from Escherichia coli repair proteins from glycation by methylglyoxal and glyoxal.

  Abdallah J., Mihoub M., Gautier V., Richarme G.

  YhbO and YajL belong to the PfpI/Hsp31/DJ-1 superfamily. Both proteins are involved in protection against environmental stresses. Here, we show that, like DJ-1 and Hsp31, they repair glyoxal- and methylglyoxal-glycated proteins. YhbO and YajL repair glycated serum albumin, collagen, glyceraldehyde ... >> More

  YhbO and YajL belong to the PfpI/Hsp31/DJ-1 superfamily. Both proteins are involved in protection against environmental stresses. Here, we show that, like DJ-1 and Hsp31, they repair glyoxal- and methylglyoxal-glycated proteins. YhbO and YajL repair glycated serum albumin, collagen, glyceraldehyde-3-phosphate dehydrogenase, and fructose biphosphate aldolase. Bacterial extracts from deglycase mutants display increased glycation levels, whereas deglycase overexpression decreases protein glycation. Moreover, yhbO and yajL mutants display decreased viability in methylglyoxal- or glucose-containing media. Finally, the apparent glyoxalase activities of YhbO and YajL reflect their deglycase activities. << Less

  Biochem. Biophys. Res. Commun. 470:282-286(2016) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Glyoxalase III from Escherichia coli: a single novel enzyme for the conversion of methylglyoxal into D-lactate without reduced glutathione.

  Misra K., Banerjee A.B., Ray S., Ray M.

  A single novel enzyme, glyoxalase III, which catalyses the conversion of methylglyoxal into D-lactate without involvement of GSH, has been detected in and purified from Escherichia coli. Of several carbonyl compounds tested, only the alpha-ketoaldehydes methylglyoxal and phenylglyoxal were found t ... >> More

  A single novel enzyme, glyoxalase III, which catalyses the conversion of methylglyoxal into D-lactate without involvement of GSH, has been detected in and purified from Escherichia coli. Of several carbonyl compounds tested, only the alpha-ketoaldehydes methylglyoxal and phenylglyoxal were found to be substrates for this enzyme. Glyoxalase III is active over a wide range of pH with no sharp pH optimum. In its native form it has an M(r) of 82000 +/-2000, and it is composed of two subunits of equal M(r). Glutathione analogues, which are inhibitors of glyoxalase I, do not inhibit glyoxalase III. Glyoxalase III is found to be sensitive to thiol-blocking reagents. The p-hydroxymercuribenzoate-inactivated enzyme could be almost completely re-activated by dithiothreitol and other thiol-group-containing compounds, indicating the possible involvement of thiol group(s) at or near the active site of the enzyme. << Less

  Biochem. J. 305:999-1003(1995) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.