title: Methylglyoxal-induced modification causes aggregation of myoglobin.
abstract: Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. We have investigated the in vitro effect of MG (200μM) on the monomeric heme protein myoglobin (Mb) (100μM) in a time-dependent manner (7 to 18days incubation at 25°C). MG induces significant structural alterations of the heme protein, including heme loss, changes in tryptophan fluorescence, decrease of α-helicity with increased β-sheet content etc. These changes occur gradually with increased period of incubation. Incubation of Mb with MG for 7days results in formation of the AGE adducts: carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87 and carboxyethyllysine or pyrraline-carboxymethyllysine at Lys-133. On increasing the period of incubation up to 14days, additional AGEs namely, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139 have been detected. MG also induces aggregation of Mb, which is clearly evident with longer period of incubation (18days), and appears to have amyloid nature. MG-derived AGEs may thus have an important role as the precursors of protein aggregation, which, in turn, may be associated with physiological complications.
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India.
authors.forename: Sauradipta
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India.
authors.forename: Subhajit
authors.initials: S
authors.lastname: Maity
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India. Electronic address: ascbmbg@caluniv.ac.in.
authors.forename: Abhay Sankar
authors.initials: AS
authors.lastname: Chakraborti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006736:Horses; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D066329:Protein Aggregates; D011487:Protein Conformation; D011765:Pyruvaldehyde / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D009211:Myoglobin; D066329:Protein Aggregates; D011765:Pyruvaldehyde
keywords: Advanced glycation end products; Amyloid structure; Methylglyoxal; Myoglobin; Protein aggregation