Abstract
Although protein consist exclusively of L-amino acids in living tissues, biologically uncommon D-aspartyl (D-Asp) residues have been detected in various proteins of metabolically inert tissues where the oxidative stress and the effect of UV irradiation are present such as eye lenses, the eye macular, skin, ligament, aorta, brain and lung. We found that Asp58 and Asp151 residues highly were inverted to D-isomers in elderly donors αA-crystallin from lenses. D-Asp occurs via a succinimide intermediate by attack of the nitrogen of the amino acid residue following the Asp residue. When the neighboring amino acid of the Asp residue has a small side chain, the formation of succinimide occurs easily because there is no steric hindrance. Therefore, L-Asp easily converts to D-Asp when the next amino acids are glycine, alanine or serine. Actually, the next amino acids of the two different sites of D-Asp in αA-crystallin were alanine and serine residues, respectively. Recently, we also found D-Asp in protein of the elastic fibers of skin from elderly donors and that the formation of D-Asp in protein is accelerated by sunlight exposure. The appearance of D-Asp in protein would induce a big change of the higher order structure of the protein because the configuration of the Asp residue would be opposite against peptide plane. In addition to D-Asp formation, beta-linkage of Asp formation affects a quaternary structure of protein because the main chain of the protein would be elongated. In this presentation, we demonstrate that this uncommon configuration of Asp by oxidative stress is considered to be one of the trigger of the abnormal aggregation of protein and it induces the related disease, such as cataract, age-related maculopathy, arteriosclerosis, solar elastosis, and Alzheimer's disease.
