D-β-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage.

Kenzo Aki,Emiko Okamura

doi:10.1038/srep21594

Abstract

Although L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. In particular, D-β-Asp is thought to be stable than any other Asp isomers, and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. It is predicted that D-β-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-β-Asp is expected to bond cleavage, although such information has not been provided yet. In this work, the spontaneous peptide bond cleavage was compared between Asp isomers, by applying real-time solution-state NMR to eye lens αΑ-crystallin 51–60 fragment, S51LFRTVLD58SG60 and αΒ-crystallin 61–67 analog, F61D62TGLSG67 consisting of L-α- and D-β-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-β-Asp residue was against the peptide bond cleavage as compared to natural L-α-Asp. Differences in pKa and conformation between L-α- and D-β-Asp side chains were plausible factors to determine reactivity of Asp isomers. The present study, for the first time, provides a rationale to explain less reactivity of D-β-Asp to allow abnormal accumulation.

Highlights

L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues
D-Asp is produced by racemization of natural L-Asp residue, the racemization accompanied by isomerization from natural α -Asp to uncommon β -Asp via a succinimide intermediate[13]
As described in the previous section, we demonstrated that uncommon D-β -Asp was less active to peptide bond cleavage than L-α -Asp residue

Summary

Introduction

L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. D-β-Asp is thought to be stable than any other Asp isomers, and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. If we consider these pathways, D-β -Asp residue is thought to be stable than any other Asp isomers (L-α -, L-β -, and D-α -Asp) This could be a most plausible reason for the gradual accumulation of D-β -Asp residue in a variety of proteins and peptides[14,15]. If peptide bonds get high resistance to the cleavage reaction, unusual amino acid residues gradually accumulate in a living body to allow abnormal stage of protein structures and functions. Notice that Cα-Cβ axes of L-α - and D-β -Asp side chains are rotated

Methods

Results

Conclusion