[omega]-Turn: A novel [beta]-turn mimic in globular proteins stabilized by main-chain to side-chain CH···O interaction

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain CO in a [beta]-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the NH component of hydrogen bond can be replaced by a C[gamma]-H group in the side chain, culminating in a nonconventional CH···O interaction. Because of its shape this [beta]-turn mimic is designated as [omega]-turn, which is found to occur three times per 100 residues. Three residues (i to i+2) constitute the turn with the CH···O interaction occurring between the terminal residues, constraining the torsion angles i+1, ψi+1, i+2 and χ'1(i+2) (using the interacting C[gamma] atom). Based on these angles there are two types of [omega]-turns, each of which can be further divided into two groups. C[beta]-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 [omega]-turn, which may be the recognition site for protein modification. Location between two [beta]-strands is the most common occurrence in protein tertiary structure, and being generally exposed [omega]-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. Proteins 2015; 83:203-214. © 2014 Wiley Periodicals, Inc.