Emerging role of carbonyl-carbonyl interactions in the classification of beta turns

Abstract

Carbonyl-carbonyl interactions in peptides and proteins attracted considerable interest in recent years. Here, we report a survey of carbonyl-carbonyl interactions in cyclic peptides, depsipeptides, peptoids and discuss the relationship between backbone torsion angles and CO∙∙∙CO distances. In general, φ values in the range between -40° and -90° and between 40° and 90° correspond to CO∙∙∙CO distances below 3.22 Å. By extending the analysis of carbonyl-carbonyl interactions in different types of beta turns in proteins, we also highlight the role of direct or reciprocal carbonyl-carbonyl interactions in stabilizing the beta turn conformation for each specific type. We confirmed the new type II beta turn, detected by Dunbrack and coworkers, and named Pa, and detect the presence of a direct carbonyl-carbonyl interaction between the second and third residues of the turn. We also evidenced the existence of another new type II beta turn, named pA (following Dunbrack's notation), which represents the alternative conformation of Pa with opposite φ and ψ values and is characterized by a direct carbonyl-carbonyl interaction between the second and third residues of the turn. Finally, we show that the occurrence of CO∙∙∙CO interactions could be also advocated to explain from a chemical point of view the diversity of turn types.

Keywords: backbone torsion angles; beta turns; carbonyl-carbonyl interactions; peptoids; protein structure; secondary structures.

FIGURE 1

Schematic representation of carbonyl to carbonyl (CO∙∙∙CO) interactions and hydrogen bonding in beta turns. O _i ∙∙∙C _i+1, O _i+1∙∙∙C _i+2, O _i+2∙∙∙C _i+3 distances are highlighted in green and C _i ∙∙∙O _i+1, C _i+1∙∙∙O _i+2, C _i+2∙∙∙O _i+3 in yellow, CO _i ∙∙∙NH _i+3 H‐bond distance is shown as a blue‐dotted line. Atom types: C gray, O red, N blue.

FIGURE 2

Beta turn mimic peptide compounds as (a) cyclic peptides, (b) depsipeptides, and (c) peptoids. X = C or N or O atoms. If X = N, then R₁′, R₂′, R₃′, R₄′, R₅′, R₆′ may also indicate a hydrogen atom; if X = O, then R₁′, R₂′, R₃′, R₄′, R₅′, R₆′ is null.

FIGURE 3

Shortest CO∙∙∙CO distance (Å) versus φ angle (°) in cyclic peptides, depsipeptides, and peptoids for left‐handed turns (negative φ values) and right‐handed turns (positive φ values), respectively.

FIGURE 4

Values distribution for shortest CO∙∙∙CO distances (Å) in cyclic peptides, depsipeptides, and peptoids.

FIGURE 5

Shortest CO∙∙∙CO distances (Å) versus φ (°) in cyclic peptides, depsipeptides, and peptoids for (A) cis and (B) trans residues.

FIGURE 6

CO∙∙∙CO distances (Å) versus φ values (°) for residues with reciprocal CO∙∙∙CO interactions, that is, both O _i ‧‧C _i+1 (blue circles) and C _i ∙∙∙O _i+1 (red circles) ≤3.22 Å.

FIGURE 7

Histogram of O _i+1∙∙∙C _i+2 distances and φ _i+2 angle for type II′ (pD) beta turns.

FIGURE 8

Scatterplot of O _i ∙∙∙C _i+1, C _i ∙∙∙O _i+1 and CO _i ∙∙∙NH _i+3 distances (Å) for Type PcisD (VI_a1) beta turn.

FIGURE 9

PCA biplot for type VI beta turns: BcisP (VI_b, red dots), PcisD (VI_a1, green dots), and PcisP (VI_b_new, blue dots). Brown arrows represent the eigenvectors of the interatomic distances.

FIGURE 10

PCA biplot for type VIII beta turns: AB1 (red), AB2 (green), AG (blue), and AZ (violet). Brown arrows represent the interatomic distances eigenvectors.