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

Brian Lyons, Joanne F. Jamie, Roger J W Truscott*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalAmino Acids
Volume46
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint Dive into the research topics of 'Separate mechanisms for age-related truncation and racemisation of peptide-bound serine'. Together they form a unique fingerprint.

Cite this