title: Age-dependent modification of proteins: N-terminal racemization.
abstract: Age-dependent deterioration of long-lived proteins in humans may have wide-ranging effects on health, fitness and diseases of the elderly. To a large extent, denaturation of old proteins appears to result from the intrinsic instability of certain amino acids; however, these reactions are incompletely understood. One method to investigate these reactions involves exposing peptides to elevated temperatures at physiological pH. Incubation of PFHSPSY, which corresponds to a region of human αB-crystallin that is susceptible to age-related modification, resulted in the appearance of a major product. NMR spectroscopy confirmed that this novel peptide formed via racemization of the N-terminal Pro. This phenomenon was not confined to Pro, because peptides with N-terminal Ser and Ala residues also underwent racemization. As N-terminal racemization occurred at 37 °C, a long-lived protein was examined. LC-MS/MS analysis revealed that approximately one third of aquaporin 0 polypeptides in the centre of aged human lenses were racemized at the N-terminal methionine.
authors: Save Sight Institute, University of Sydney, Sydney Eye Hospital, NSW, Australia.
authors: Brian
authors: B
authors: Lyons
authors: Ann H
authors: AH
authors: Kwan
authors: Joanne
authors: J
authors: Jamie
authors: Roger J W
authors: RJ
authors: Truscott
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000595:Amino Acid Sequence; D020346:Aquaporins / Q000737:chemistry* / Q000378:metabolism*; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D007908:Lens, Crystalline / Q000378:metabolism; D008715:Methionine / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053719:Tandem Mass Spectrometry; D038203:alpha-Crystallin B Chain / Q000737:chemistry*
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D010446:Peptide Fragments; D038203:alpha-Crystallin B Chain; C030328:aquaporin 0; D011392:Proline; D008715:Methionine