title: Methylglyoxal-induced modifications of hemoglobin: structural and functional characteristics.
abstract: Methylglyoxal (MG) reacts with proteins to form advanced glycation end products (AGEs). Although hemoglobin modification by MG is known, the modified protein is not yet characterized. We have studied the nature of AGE formed by MG on human hemoglobin (HbA(0)) and its effect on structure and function of the protein. After reaction of HbA(0) with MG, the modified protein (MG-Hb) was separated and its properties were compared with those of the unmodified protein HbA(0). As shown by MALDI-mass spectrometry, MG converted Arg-92α and Arg-104β to hydroimidazolones in MG-Hb. Compared to HbA(0), MG-Hb exhibited decreased absorbance around 280nm, reduced tryptophan fluorescence (excitation 285nm) and increased α-helix content. However, MG modification did not change the quaternary structure of the heme protein. MG-Hb appeared to be more thermolabile than HbA(0). The modified protein was found to be more effective than HbA(0) in H(2)O(2)-mediated iron release and oxidative damages involving Fenton reaction. MG-Hb exhibited less peroxidase activity and more esterase activity than HbA(0). MG-induced structural and functional changes of hemoglobin may enhance oxidative stress and associated complications, particularly in diabetes mellitus with increased level of MG.
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta 92, Acharya Prafulla Chandra Road, Kolkata 700 009, India.
authors.forename: Tania
authors.initials: T
authors.lastname: Bose
authors.forename: Abhishek
authors.initials: A
authors.lastname: Bhattacherjee
authors.forename: Sauradipta
authors.initials: S
authors.lastname: Banerjee
authors.forename: Abhay Sankar
authors.initials: AS
authors.lastname: Chakraborti
mesh_terms: D001665:Binding Sites; D006454:Hemoglobins / Q000737:chemistry* / Q000648:ultrastructure*; D006801:Humans; D011485:Protein Binding; D011765:Pyruvaldehyde / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D006454:Hemoglobins; D011765:Pyruvaldehyde