Computational studies on non-succinimide-mediated stereoinversion mechanism of aspartic acid residues assisted by phosphate. (19th March 2018)

• Record Type: Journal Article
• Authors: Nakayoshi, Tomoki; Fukuyoshi, Shuichi; Takahashi, Ohgi; Oda, Akifumi
• Is Part Of: Molecular physics. Volume 116:Number 5/6(2018)
• Page Start: 686
• Page End: 696
• Publication Date: 2018-03-19
• Subjects: Aspartic acid residue -- stereoinversion -- non-enzymatic reaction -- phosphate-catalysed -- density functional theory; Molecules -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Molécules -- Périodiques; Chimie physique et théorique -- Périodiques; 539.6.05
• DOI: 10.1080/00268976.2017.1414964
• Languages: English
• ISSNs: 0026-8976

Abstract

ABSTRACT: Although nearly all of the amino acids that constitute proteins arel -amino acids, d -amino acid residues in human proteins have been recently reported.d -amino acid residues cause a change in the three-dimensional structure of proteins, andd -aspartic acid (Asp) residues are considered to be one of the causes of age-related diseases. The stereoinversion of Asp residues in peptides and proteins is thought to proceed via a succinimide intermediate; however, it has been reported that stereoinversion can occur even under conditions where a succinimide intermediate cannot be formed. In order to elucidate the non-succinimide-mediated stereoinversion pathway, we investigated the stereoinversion ofl -Asp tod -Asp catalysed by phosphate and estimated the activation barrier using B3LYP/6−31+G(d, p) density functional theory (DFT) calculations. For the DFT calculations, a model compound in which the Asp residue is capped with acetyl and methyl-amino groups on the N- and C-termini, respectively, was used. The calculated activation barrier was not excessively high for the stereoinversion to occur in vivo . Therefore, this stereoinversion mechanism may compete with the succinimide-mediated mechanism. GRAPHICAL ABSTRACT: