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

Abstract

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

Keywords:

• Hen egg white lysozyme
• Methylglyoxal
• Advanced Glycation End Products
• amyloid
• Mass spectrometry

Acknowledgements

S.B. duly acknowledges Prof. Jyotirmayee Dash (School of Chemical Sciences, Indian Association for the Cultivation of Sciences) for providing necessary laboratory facilities and extensive support in conducting the research work. In addition, the central instrumentation facility of Indian Association for the Cultivation of Sciences is highly acknowledged. S.B. is especially thankful to Mr. Sanjib Naskar, Mrs. Champa Bag and Mr. Arup Bandyopadhyay for their kind help and cooperation in performing AFM, DLS and DSC experiments, respectively.

Disclosure statement

The author declares that there is no potential conflict of interest associated with the study.

Additional information

Funding

S.B. duly acknowledges Indian Council of Medical Research (File No. 2019-3694/GEN-BMS) for their financial support in conducting the study.