Methylglyoxal modification reduces the sensitivity of hen egg white lysozyme to stress-induced aggregation: Insight into the anti-amyloidogenic property of α-dicarbonyl compound.

The reactive α-oxoaldehyde, methylglyoxal reacts with different proteins to form Advanced Glycation End Products (AGEs) through Maillard reaction. Its level increases significantly in diabetic condition. Here, we have investigated the effect of different concentrations of methylglyoxal (200-400 µM) on the monomeric protein, hen egg white lysozyme (HEWL) following incubation for 3 weeks. Reaction of methylglyoxal with HEWL induced considerable changes in tertiary structure of the protein, but no significant alteration in secondary structure, as evident from different spectroscopic and biophysical studies. Interestingly, methylglyoxal modification was found to enhance the thermal stability of the protein and reduce its sensitivity to stress-induced aggregation. Finally, peptide mass fingerprinting revealed modification of arginine (Arg-45, Arg-14, Arg-68 or Arg-72) and lysine (Lys-116) residues of the protein to AGE adducts, namely, hydroimidazolone, tetrahydropyrimidine, and carboxyethyllysine. Methylglyoxal-derived AGE adducts (MAGE) appear to be responsible for the observed changes in protein. As demonstrated in the present study, the findings may highlight a possible therapeutic potential of the α-oxoaldehyde against protein misfolding and conformational disorder.Communicated by Ramaswamy H. Sarma.