Bridging of partially negative atoms by hydrogen bonds from main‐chain NH groups in proteins: The crown motif

Abstract

The backbone NH groups of proteins can form N1N3-bridges to δ-ve or anionic acceptor atoms when the tripeptide in which they occur orients them appropriately, as in the RL and LR nest motifs, which have dihedral angles 1,2-αR αL and 1,2-αL αR , respectively. We searched a protein database for structures with backbone N1N3-bridging to anionic atoms of the polypeptide chain and found that RL and LR nests together accounted for 92% of examples found (88% RL nests, 4% LR nests). Almost all the remaining 8% of N1N3-bridges were found within a third tripeptide motif which has not been described previously. We term this a "crown," because of the disposition of the tripeptide CO groups relative to the three NH groups and the acceptor oxygen anion, and the crown together with its bridged anion we term a "crown bridge." At position 2 of these structures the dihedral angles have a tight αR distribution, but at position 1 they have a wider distribution, with ϕ and ψ values generally being lower than those at position 1. Over half of crown bridges involve the backbone CO group three residues N-terminal to the tripeptide, the remainder being to other main-chain or side-chain carbonyl groups. As with nests, bridging of crowns to oxygen atoms within ligands was observed, as was bridging to the sulfur atom of an iron-sulfur cluster. This latter property may be of significance for protein evolution.

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

“…We propose an alternative explanation, in which the preference for α-helical binding sites in the ancient phosphate binders is a reflection of the constraints acting on the earliest proteins: Assuming short, prebiotic sequences, the N-helix is the most accessible solution to phosphate binding (this explanation may be complementary rather than contradictory to the common ancestry one). The prevalence of bidentate interactions at the N-helix underscores the importance of forming a "crown" of hydrogen bonds (8,51), as opposed to the helix dipole (52), as previously suggested (11).…”

ExploreTurns: A web tool for the exploration, analysis, and classification of beta turns and structured loops in proteins; application to beta-bulge and Schellman loops, Asx helix caps, beta hairpins and other hydrogen-bonded motifs

“…ExploreTurns enables the analysis and retrieval of sets of examples of any BB motif that can be defined by the tool's selection criteria operating on a twelve-residue window centered on a beta burn, including many types of beta hairpins 14,15 , supersecondary structures in which beta turns link helices/strands into particular geometries, some beta bulges 16 and nests 17 , and all types of short H-bonded loops known to the author, including the alpha-beta loop 8 , beta-bulge loops 11 , crown bridge loop 18 , BB mediated helix caps such as the Schellman loop 19,20,21,22 and its variants, and others (Supplementary Section 2).…”

Protein three-dimensional structures at the origin of life

“…It is worth adding that tripeptide motifs called crowns that bind anions or δ-atoms in the same way as nests, but with all ϕ and ψ angles negative for the first two residues, have been described [16]. They are far less abundant than nests but should be distinguished from them.…”