Inversion and isomerization of Asp-58 residue in human alphaA-crystallin from normal aged lenses and cataractous lenses.
We have previously shown that L-Asp-151 in alphaA-crystallin from the human lens is converted to the biologically uncommon D-isomer. This process was not simple racemization, but stereoinversion, accompanied by isomerization to form the beta-Asp residue, such that L-beta-Asp, D-alpha-Asp and D-beta-Asp were formed. The present study shows that Asp-58 of human alphaA-crystallin is also converted to the D-isomer to a high degree to form the same isomers with age. The D/L ratio of beta-Asp-58 in aged normal lens increased to more than 3.0, showing stereoinversion by the 60 year range, then decreased to 1.0 in the 80 year range, while the isomerization of Asp-58 increased in the 80 year range. We also measured inversion and isomerization of the same residue from cataractous and normal human lenses of the 60 year range. The D/L ratio of Asp-58 from cataractous lenses was significantly lower than that from normal lenses, while the isomerization at Asp-58 in cataractous alphaA-crystallin was significantly higher than that of normal alphaA-crystallin. These results indicate that isomerization to the beta isomer of Asp-58 in cataractous alphaA-crystallin increased more than inversion to the D-isomer, suggesting that there are changes in the native structure of alphaA-crystallin in the human cataractous lens.
Fujii
N
N
Research Reactor Institute, Kyoto University, Sennan, Osaka, Japan. nfujii@hl.rri.kyoto-u.ac.jp
Matsumoto
S
S
Hiroki
K
K
Takemoto
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001224:Aspartic Acid / Q000737:chemistry*; D002386:Cataract / Q000503:physiopathology*; D003459:Crystallins / Q000737:chemistry*; D006801:Humans; D007223:Infant; D007536:Isomerism; D007908:Lens, Crystalline / Q000737:chemistry* / Q000503:physiopathology; D008875:Middle Aged; D008956:Models, Chemical; D017510:Protein Folding; D013237:Stereoisomerism
D003459:Crystallins; D001224:Aspartic Acid