ANION-BINDING SITES IN PROTEIN STRUCTURES

An analysis of the binding of 52 sulfate and phosphate ions in 34 protein structures has been carried out. On average an oxyanion is held by 7(±3) hydrogen bonds, of which the contribution of the protein is 5(±3) (the rest coming from water). Arg and the peptide NH group are the most common ligands, other basic and polar side-chains, including Asp and Glu, have their own shares. The negative charge on the ion is not neutralized by the protein in all the cases. The geometry of the ligand (L) with reference to a SO4 or PO4 is such that the angle S/P-O L is 128(±15)° and 96(±15)° for the two classes of interactions distinguished by the existence of only one or more than one hydrogen bond connecting the ligand atom and the anion. The binding belonging to the former category is usually in a staggered orientation with respect to the anion-tetrahedron; those in the latter class are close to the eclipsed conformation. An anion is held in a very limited space close to the NH direction of a peptide group; the strongly localized nature of the interaction imparts rigidity to the binding. Both local steric and electrostatic elements favor the peptide group to be at the N terminus of a helix. Additional ligands can be supplied by the polypeptide chain preceding the helical N terminus. β-Turns are also propitious for the location of ligands. There are patterns in the binary and ternary interactions involving various anions. One of the constituents of the ligand peptide group is likely to be a Gly; with no side-chain this residue offers the minimum steric hindrance to the bound anion. In 50% of the cases with a Ser, a Thr or a basic residue occupying one of these positions, the side-chain also acts as a hydrogen bond donor. Gly is also likely to occur next to a side-chain ligand located in a β-turn. About a third of the anions have ligands from a crystallographic or molecular symmetry-related position. © 1993 Academic Press Limited.