Effects of Lysine Acetylation in a β-Hairpin Peptide: Comparison of an Amide−π and a Cation−π Interaction

Abstract

The acetylation of lysine is a common posttranslational modification of histone proteins, and the interaction of acetylated lysines with aromatic rings is commonly observed in transcriptionally relevant protein-protein interactions. To determine the nature of this interaction and its potential role in protein structure and function, the effect of lysine acetylation on its interaction with tryptophan has been investigated within the context of a beta-hairpin peptide. Acetylation of Lys results in the replacement of a cation-pi interaction with an amide-pi interaction. Despite the loss of positive charge, the interaction energy is not significantly perturbed, although the geometry of interaction is influenced such that the amide NH interacts directly with the Trp ring. Thermodynamic analysis indicates an enthalpic driving force for the stabilization, indicating a polar-pi interaction. Acyl lysine analogues formyl lysine and trifluoroacetyl lysine were used to further investigate the sterics and electronics of the interaction.