A recurring two-hydrogen-bond motif incorporating a serine or threonine residue is found both at alpha-helical N termini and in other situations.

Side-chain hydroxyl residues in protein crystal structures often form hydrogen bonds with main-chain atoms. The most common bond arrangement is a four to five residue motif in which a serine or threonine is the first residue forming two characteristic hydrogen bonds to residues ahead of it in sequence. We call them ST-motifs, by analogy with the term Asx-motif we suggested for the related motifs with aspartate and asparagine residues. ST-motifs are common, there being just under one and a half in a typical protein subunit. Asx-motifs are even more common, such that 9 % of the residues of an average protein consist of Asx or ST-motifs. Of the ST-motifs, three-quarters are at helical N termini, and the rest occur by themselves or in conjunction with beta-bulge loops. A third of all alpha-helices have either ST-motifs or Asx-motifs at their N termini. Previous work has emphasised the occurrence of the capping box at alpha-helical N termini, but the capping box occurs in only 5 % of alpha-helical N termini; also, we point out that it can be regarded as a subset of the ST-motif (or, occasionally, of the Asx-motif). By comparing related sequences, the rates which amino acid residues at the first position of ST or Asx-motifs interchange during evolution are examined. Serine <==> threonine, and aspartate <==> asparagine, interchange is rapid; inter-pair exchange is slower, but much faster than exchange with other amino acid residues. This is consistent with the general similarity of ST-motifs and Asx-motifs combined with some subtle structural differences between them that are described. Copyright 1999 Academic Press.