Abstract
Despite the known racemization of serine (Ser) residues in proteins from aged or diseased human brains, the mechanism of Ser racemization in peptides and proteins has not been studied. This is in contrast to the case of the rapid racemization of aspartic acid (Asp) residues, for which a succinimide-mediated mechanism is established. In a possible mechanism for Ser racemization, the enolization involving the H(alpha)-atom and the CO(alpha) group occurs by active participation of two H(2)O molecules. In this study, we computationally modeled this two-H(2)O mechanism of enolization for Ser and alanine (Ala) residues using model compounds, and the results were compared with each other and with the case of succinimide analogues reported in a separated paper. Our results suggest that Ser residues are much more racemization-prone than Ala residues, but to a lesser extent than Asp residues. The side-chain C-O bond of the Ser residue stabilizes the enolization transition state hyperconjugatively.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
