An electronic effect on protein structure

Abstract

The well‐known preference of the peptide bond for the trans conformation has been attributed to steric effects. Here, we show that a proline residue with an N ‐formyl group (H i −1 −C′ i −1 =O i −1 ), in which H i −1 presents less steric hindrance than does O i −1 , likewise prefers a trans conformation. Thus, the preference of the peptide bond for the trans conformation cannot be explained by steric effects alone. Rather, an n → π* interaction between the oxygen of the peptide bond (O i −1 ), and the subsequent carbonyl carbon in the polypeptide chain (C′ i ) also contributes to this preference. The O i −1 and C′ i distance and O i −1 ···C′ i =O i angle are especially favorable for such an n → π* interaction in a polyproline II helix. We propose that this electronic effect provides substantial stabilization to this and other elements of protein structure.