D-Amino Acid Formation Induced by a Chiral Field within a Human Lens Protein during Aging

Abstract

We have previously shown that Asp-151 in αA-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 αA-crystallin has a chiral reaction field which promotes the inversion of L-Asp to D-Asp residues in the native higher order structure of αA-crystallin itself. Here, we show that when the aged human αA-crystallin, enriched at Asp-151 with the D-isomer (D/L ratio of 5.7), was unfolded by heating at 70°C or 6 M urea, the D-Asp-151 in the unfolded αA-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.