title: The structural feature surrounding glycated lysine residues in human hemoglobin.
abstract: Complications derived from diabetes mellitus are caused by nonenzymatic protein glycation at the specific sites. LC/MS/MS was performed for the identification of the tryptic peptides of glycated hemoglobins using glyceraldehyde. After the identification of the glycation or non-glycation site, computer analysis of the structure surrounding the sites was carried out using PDB data (1BZ0). Five glycated lysine residues (Lys-16(α), -56(α), -8(β), -82(β), and -144(β)) and four non-glycated lysine residues (Lys-7(α), -40(α), -99(α), and -132(β)) were identified. The non-glycated lysine residues, Lys-7(α), -40(α), and -132(β), are most likely to form electrostatic interactions with the β carboxyl group of Asp-74(α), C-terminal His-146(β), and Glu-7(β) by virtue of their proximity, which is 2.67-2.91 Å (N-O). Additionally, there are histidine residues within 4.55-7.38 Å (N-N) around eight sites except for Lys-7(α). We conclude that the following factors seem to be necessary for glycation of lysine residues: (i) the apparent absence of aspartate or glutamate residues to inhibit the glycation reaction by forming an electrostatic interaction, (ii) the presence of histidine residues for acid-base catalysis of the Amadori rearrangement, and (iii) the presence of an amino acid residue capable of stabilizing a phosphate during proton transfer.
authors.affiliation: Department of Physiological Chemistry, Osaka Medical College, Daigakucho, Takatsuki, Japan. ito@art.osaka-med.ac.jp
authors.forename: Shigenori
authors.initials: S
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D005985:Glyceraldehyde / Q000378:metabolism; D006031:Glycosylation; D006454:Hemoglobins / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein
chemical_list: D006454:Hemoglobins; D010455:Peptides; D001224:Aspartic Acid; D005985:Glyceraldehyde; D006639:Histidine; D008239:Lysine