A novel main-chain anion-binding site in proteins: the nest. A particular combination of φ,ψ values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions

Main-chain conformations where one amino acid residue can be described as γR (or αR) and an adjacent one as γL (or αL) mostly result in the three main-chain NH groups (of the two residues and the one following) forming a depression that can accommodate an atom with a whole or partial negative charge. We propose the name nest for this feature. The negatively charged atom, when present, is also stabilized by hydrogen-bonding with the NH groups. In an average protein, 8 % of residues are involved in a nest. The anion, or partially negatively charged atom, that often occupies the nest may be a main-chain carbonyl oxygen atom as in the paperclip, also called the Schellman loop, and the oxyanion hole of serine proteases. It can be a phosphate group, as in the P-loop superfamily that binds ATP and GTP. Overlapping, compound, nests are observed often, as in the P-loop, which has five successive NH groups that bind the β phosphate group of nucleotide triphosphate. The longest compound nests are found surrounding cysteine-bound [2Fe2S] and [4Fe4S] iron-sulfur centers, which are also anionic; nests may encourage binding of the more reduced forms. The nest is a novel feature in the sense of not having been described as a unique motif with anion-binding potential before, although some of the situations where it occurs are familiar.