A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

J Mol Model. 2013 Dec;19(12):5501-13. doi: 10.1007/s00894-013-2054-y. Epub 2013 Nov 17.

Abstract

In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / chemistry*
  • Hydrolysis
  • Kinetics
  • Metabolic Networks and Pathways*
  • Models, Chemical
  • Peptides / chemistry*
  • Peptides / metabolism
  • Thermodynamics

Substances

  • Peptides
  • Aspartic Acid