title: Accelerated aging of Asp 58 in αA crystallin and human cataract formation.
abstract: Racemisation of amino acids is one of the most abundant modifications in long-lived proteins. In this study racemisation of Asp 58 in the small heat shock protein, αA crystallin, was investigated. In normal human lenses, levels of l-isoAsp, d-isoAsp and d-Asp increased with age, such that by age 70 they accounted for approximately half of the total Asp at this site. Levels of d-isoAsp were significantly higher in all cataract lenses than age-matched normal lenses. The introduction of d-isoAsp in αA crystallin could therefore be associated with the development of cataract. Its more rapid formation in cataract lenses may represent an example of accelerated protein aging leading to a human age-related disease.
authors.affiliation: Save Sight Institute, Sydney Eye Hospital, University of Sydney, 8 Macquarie Street, Sydney, New South Wales 2000, Australia.
authors.forename: Michelle Y S
authors.initials: MY
authors.lastname: Hooi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Roger J W
authors.initials: RJ
authors.lastname: Truscott
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001224:Aspartic Acid / Q000378:metabolism*; D002386:Cataract / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D026581:Isoaspartic Acid / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008875:Middle Aged; D010446:Peptide Fragments; D019998:Racemases and Epimerases; D021241:Spectrometry, Mass, Electrospray Ionization; D055815:Young Adult; D038202:alpha-Crystallin A Chain / Q000378:metabolism*
chemical_list: D026581:Isoaspartic Acid; D010446:Peptide Fragments; D038202:alpha-Crystallin A Chain; D001224:Aspartic Acid; D019998:Racemases and Epimerases