Phosphate-Catalyzed Succinimide Formation from Asp Residues: A Computational Study of the Mechanism.

ABSTRACT: Aspartic acid (Asp) residues in proteins and peptides are prone to the non-enzymatic reactions that give biologically uncommon l-β-Asp, d-Asp, and d-β-Asp residues via the cyclic succinimide intermediate (aminosuccinyl residue, Suc). These abnormal Asp residues are known to have relevance to aging and pathologies. Despite being non-enzymatic, the Suc formation is thought to require a catalyst under physiological conditions. In this study, we computationally investigated the mechanism of the Suc formation from Asp residues that were catalyzed by the dihydrogen phosphate ion, H₂PO₄-. We used Ac-l-Asp-NHMe (Ac = acetyl, NHMe = methylamino) as a model compound. The H₂PO₄- ion (as a catalyst) and two explicit water molecules (as solvent molecules stabilizing the negative charge) were included i

SUBMITTER: Kirikoshi R 

PROVIDER: S-EPMC5855859 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature