D-amino acid formation induced by a chiral field within a human lens protein during aging.
We have previously shown that Asp-151 in alphaA-crystallin from aged human lens are converted to the biologically uncommon D-isomer to a high degree, showing that the formation of D-isomer was not simple racemization, but stereoinvertion. This suggests that alphaA-crystallin has a chiral reaction field which promotes the inversion of L-Asp to D-Asp residues in the native higher order structure of alphaA-crystallin itself. Here, we show that when the aged human alphaA-crystallin, enriched at Asp-151 with the D-isomer (D/L ratio of 5.7), was unfolded by heating at 70 degrees C or 6 M urea, the D-Asp-151 in the unfolded alphaA-crystallin was rapidly racemized (D/L ratio of 2.17 to 1.21). This presumably reflects a relaxation of the chiral field that was initially inducing the stereoinversion from the natural L-isomer to the D-isomer.
Fujii
N
N
Research Reactor Institute, Kyoto University, Kumatori, Sennan, Osaka, 590-0494, Japan. nfujii@HL.rri.kyoto-u.ac.jp
Harada
K
K
Momose
Y
Y
Ishii
N
N
Akaboshi
M
M
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001224:Aspartic Acid / Q000737:chemistry*; D003459:Crystallins / Q000737:chemistry*; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry*; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017421:Sequence Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism
D003459:Crystallins; D009842:Oligopeptides; D010446:Peptide Fragments; D001224:Aspartic Acid