Kinetic study of racemization of aspartyl residues in model peptides of alpha A-crystallin.
We have reported that two aspartyl (Asp-151 and Asp-58) residues in alpha A-crystallin in human eye lens were inverted to the D-isomer and isomerized to beta-aspartyl residues with age. We report here the kinetics of the Asp racemization of three model peptides corresponding to fragments of alpha A-crystallin: IQTGLD151ATHAER (T18 peptide), TVLD58SGISEVR (T6 peptide) and HFSPED84LTVK (T10 peptide, as a control). The rate constants of the racemization of Asp residues in these peptides were measured at pH 7.0, at five temperatures: 50, 60, 70, 80 and 90 degrees C. From the Arrhenius equation, we estimated the activation energy (E) of racemization and the time required for the Asp D/L ratio to approximate to 1.0 (D/L ratio of Asp = 0.99) at body temperature. For the peptide T18, E = 21.4 kcal/mol and t = 13.5 yr. For the peptide T6, E = 26.8 kcal/mol and r = 49.5 yr. For the control peptide T10, E = 28.3 kcal/mol and t = 78.1 yr. The racemization rate of Asp in these three peptides is parallel to that of Asp residues in alpha A-crystallin. The racemization rate of Asp in the T18 peptide was very rapid compared to that in the other peptides. This result also reflects the racemization rate in native alpha A-crystallin.
Fujii
N
N
Research Development Corporation of Japan (JRDC), Ibaraki, Japan.
Momose
Y
Y
Harada
K
K
D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D003459:Crystallins / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D013237:Stereoisomerism
D003459:Crystallins; D010446:Peptide Fragments; D001224:Aspartic Acid