Formation of four isomers at the asp-151 residue of aged human alphaA-crystallin by natural aging.
Although proteins are generally composed entirely of l-amino acids, we have previously shown that Asp-151 in alphaA-crystallin from aged human lens is converted to the biologically uncommon d-isomer to a high degree. The formation of d-isomer was not simple racemization, but stereoinvertion. The reaction was also accompanied with isomerization to form beta-Asp (isoaspartate) residue simultaneously; therefore, four isomers of Asp-151, normal l-alpha-Asp and biologically uncommon l-beta-Asp, d-alpha-Asp, and d-beta-Asp, are formed in alphaA-crystallins. In the present study, we measured the ratio of the four isomers of Asp-151 in alphaA-crystallins obtained from total lens proteins of human lenses of newborn and 30-, 60-, and 80-year-olds. The isomers increased with age, and the total amount of three isomers was more than that of normal l-alpha-Asp in the alphaA-crystallin of the human lenses of the 80-year-olds. These drastic changes started at birth, with about 45% of normal l-alpha-Asp lost by 30 years. These modifications of the Asp residue likely affect the three-dimensional packing array of the lens proteins.
Fujii
N
N
Research Reactor Institute, Kyoto University, Sennan, Osaka, 590-0494, Japan. nfujii@HL.rri.kyoto-u.ac.jp
Takemoto
L J
LJ
Momose
Y
Y
Matsumoto
S
S
Hiroki
K
K
Akaboshi
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001224:Aspartic Acid / Q000737:chemistry; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008875:Middle Aged; D008956:Models, Chemical; D013237:Stereoisomerism
D003459:Crystallins; D001224:Aspartic Acid