Amino Acids

, Volume 46, Issue 1, pp 199–207

Separate mechanisms for age-related truncation and racemisation of peptide-bound serine

  • Brian Lyons
  • Joanne F. Jamie
  • Roger J. W. Truscott
Original Article


Some amino acids are particularly susceptible to degradation in long-lived proteins. Foremost among these are asparagine, aspartic acid and serine. In the case of serine residues, cleavage of the peptide bond on the N-terminal side, as well as racemisation, has been observed. To investigate the role of the hydroxyl group, and whether cleavage and racemisation are linked by a common mechanism, serine peptides with a free hydroxyl group were compared to analogous peptides where the serine hydroxyl group was methylated. Peptide bond cleavage adjacent to serine was increased when the hydroxyl group was present, and this was particularly noticeable when it was present as the hydroxide ion. Adjacent amino acid residues also had a pronounced affect on cleavage at basic pH, with the SerPro motif being especially susceptible to scission. Methylation of the serine hydroxyl group abolished truncation, as did insertion of a bulky amino acid on the N-terminal side of serine. By contrast, racemisation of serine occurred to a similar extent in both O-methylated and unmodified peptides. On the basis of these data, it appears that racemisation of Ser, and cleavage adjacent to serine, occur via separate mechanisms. Addition of water across the double bond of dehydroalanine was not detected, suggesting that this mechanism was unlikely to be responsible for conversion of l-serine to d-serine. Abstraction of the alpha proton may account for the majority of racemisation of serine in proteins.


Serine Truncation Racemisation Aging Post translational modification Dehydroalanine 



O-Methyl ether







Supplementary material

726_2013_1619_MOESM1_ESM.tif (1.5 mb)
Supplementary Figure 1A: Truncation at N-terminal side of Ser as a function of time. Cleavage was calculated based on the amount of Ac-AA formed compared to the amount of each peptide present at time = 0. Peptides were incubated in sodium borate buffer (100 mM, pH 12.5) at 37 °C. (A) = Ac-AASAA and Ac-AAPSAA. (TIFF 1561 kb)
726_2013_1619_MOESM2_ESM.tif (1.5 mb)
Supplementary Figure 1B: Truncation at N-terminal side of Ser as a function of time. Cleavage was calculated based on the amount of Ac-AA formed compared to the amount of each peptide present at time = 0. Peptides were incubated in sodium borate buffer (100 mM, pH 12.5) at 37 °C (B) = Ac-AASAA and Ac-AALSAA.(TIFF 1563 kb)


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Brian Lyons
    • 1
  • Joanne F. Jamie
    • 2
  • Roger J. W. Truscott
    • 3
  1. 1.Save Sight Institute, Sydney Eye HospitalUniversity of SydneySydneyAustralia
  2. 2.Department of Chemistry and Biomolecular SciencesMacquarie UniversitySydneyAustralia
  3. 3.Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia

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