ω-Turn: A novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C-H···O interaction

Abstract

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C=O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the N-H component of hydrogen bond can be replaced by a Cγ-H group in the side chain, culminating in a nonconventional C-H···O interaction. Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼three times per 100 residues. Three residues (i to i+2) constitute the turn with the C-H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi+1, ψi+1, ϕi+2 and χ′1(i+2) (using the interacting Cγ atom). Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. Cβ-branched side-chains, and Met and Gln have high propensities to occur at i+2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i+1 position, such turns are found in the metal-binding sites. N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i+2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design.