The effect of oxidative stress on the bursopentin peptide structure: a theoretical study

Bursopentin (BP5, H-Cys1-Lys2-Arg3-Val4-Tyr5-OH), found in the bursa Fabricius of the chicken, is a pentapeptide that protects the organism from oxidative stress by reducing the intracellular generation of reactive oxygen species. Hydrogen abstraction, a common oxidative reaction occurring in proteins, often results in the formation of D amino acid residues. To study the effect of this phenomenon on the structure of bursopentin, each of its residues were converted from the L configuration to the D configuration, and the structures of these peptide epimers were compared to that of the wild-type bursopentin. The conformations, secondary structures, compactness and hydrogen bonding of bursopentin were compared to its epimers using molecular dynamics simulations and first principles quantum chemical computations. It was discovered that the repulsion between the side chains of Lys2 and Arg3 influenced the conformation of the peptide regardless of the configuration of these residues. Epimerisation of the Val4 and Tyr5 caused a reduction in the compactness of bursopentin. In all cases, the occurrence of a turn structure was relatively high, especially when Arg3 was in the D configuration. Thermodynamic analysis of the epimerisation process showed that the formation of D amino acid residues is favourable.