D-amino acid formation induced by a chiral field within a human lens protein during aging

We have previously shown that Asp-151 in alpha A-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 alpha A-crystallin has a chiral reaction field which pro motes the inversion of L-Asp to D-Asp residues in the native higher order structure of alpha A-crystallin itself, Here, we show that when the aged human alpha A-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 alpha A-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. (C) 1999 Academic Press.