7 research outputs found
The geometry and efficacy of cationâĎ interactions in a diagonal position of a designed β-hairpin
CationâĎ interactions are common in proteins, but their contribution to the stability and specificity of protein structure has not been well established. In this study, we examined the impact of cationâĎ interactions in a diagonal position of a β-hairpin peptide through comparison of the interaction of Phe or Trp with Lys or Arg. The diagonal interactions ranged from â0.20 to â0.48 kcal/mole. Our experimental values for the diagonal cationâĎ interactions are similar to those found in Îą-helical studies. Upfield shifting of the Lys and Arg side chains indicates that the geometries of cationâĎ interactions adopted in the 12-residue β-hairpin are comparable to those found in protein structures. The Lys was found to interact through the polarized CÉ, and the Arg is stacked against the aromatic ring of Phe or Trp. Folding of these peptides was found to be enthalpically favorable (ÎH° âź â3 kcal/mole) and entropically unfavorable (ÎS°⟠â8 cal moleâ1 Kâ1)
Investigation of the nature of the methionineâĎ interaction in β-hairpin peptide model systems
There are frequent contacts between aromatic rings and sulfur atoms in proteins. However, it is unclear to what degree this putative interaction is stabilizing and what the nature of the interaction is. We have investigated the arylâsulfur interaction by placing a methionine residue diagonal to an aromatic ring on the same face of a β-hairpin, which places the methionine side chain in close proximity to the aryl side chain. The methionine (Met)âaryl interaction was compared with an equivalent hydrophobic and cationâĎ interaction in the context of the β-hairpin. The interaction between phenylalanine (Phe), tryptophan (Trp), or cyclohexylalanine (Cha) and Met stabilized the β-hairpin by â0.3 to â0.5 kcal moleâ1, as determined by double-mutant cycles. The peptides were subjected to thermal denaturations that suggest a hydrophobic driving force for the interactions between Met and Trp or Cha. The observed interaction of Met or norleucine (Nle) with Trp or Cha are quite similar, implying a hydrophobic driving force for the MetâĎ interaction. However, the thermodynamic data suggest that there may be some differences between the interaction of Met with Trp and Phe and that there may be a small thermodynamic component to the Metâ˘â˘â˘Phe interaction