omega -Turn: A novel beta -turn mimic in globular proteins stabilized by main-chain to side-chain C--H...O interaction

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C==O in a beta -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 C super( gamma )-H group in the side chain, culminating in a nonconventional C--H...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 C--H...O interaction occurring between the terminal residues, constraining the torsion angles sub(i) sub(+1), psi sub(i) sub(+1), sub(i) sub(+2) and chi ' sub(1() sub(i) sub(+2)) (using the interacting C super( gamma ) atom). Based on these angles there are two types of omega -turns, each of which can be further divided into two groups. C super( 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. copyright 2014 Wiley Periodicals, Inc.