Comparison of the activation energy barrier for succinimide formation from α- and β-aspartic acid residues obtained from density functional theory calculations

In this study, we computationally investigated the cyclization of α- and β-Asp residues to form succinimide with dihydrogen phosphate ion as a catalyst (H2PO4 −). We performed the study using B3LYP/6–31+G(d,p) density functional theory calculations. The comparison of the activation barriers of both residues is discussed. All the calculations were performed using model compounds in which an α/β-Asp-Gly sequence is capped with acetyl and methylamino groups on the N- and C-termini, respectively. Moreover, H2PO4 − catalyzes all the steps of the succinimide formation (cyclization-dehydration) acting as a proton-relay mediator. The calculated activation energy barriers for succinimide formation of α- and β-Asp residues are 26.9 and 26.0kcal mol−1, respectively. Although it was experimentally confirmed that β-Asp has higher stability than α-Asp, there was no clear difference between the activation barriers. Therefore, the higher stability of β-Asp residue than α-Asp residue may be caused by an entropic effect associated with the succinimide formation. Graphical abstract

Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - January 3, 2018 Category: Biochemistry Source Type: research