BIOLOGICAL COORDINATION CHEMISTRY OF MAGNESIUM, SODIUM, AND POTASSIUM-IONS - PROTEIN AND NUCLEOTIDE-BINDING SITES

In this article, we review the structural chemistry of the alkali and alkaline earth metal cations (Mg2+, Na+, and K+) with three classes of biological macromolecule (proteins, nucleic acids, and membrane lipids). Emphasis is placed on crystallographically well-characterized examples that illustrate the characteristic features of ligand type and coordination geometry that define the binding specificity and functional role (structural or catalytic) of these co-factors. Reflecting the availability of literature data, the focus of the review is directed toward magnesium chemistry. Four classes of magnesium coordination site (A-D) are defined according to whether the co-factor interacts predominantly with the protein or substrate, and serves either a structural or catalytic role. The distinction between inner and outer coordination modes is made. There is an apparent tendency for magnesium to bind to nucleic acids by extensive hydrogen bonding from waters of hydration to heteroatoms on bases and the ribose-phosphate backbone, while inner-sphere binding to proteins is promoted by the well-defined chelating pockets defined by protein residues. With regard to the functional role of the metal, the lability of these metal cofactors must be considered in the context of enzyme mechanism, inasmuch as the most stable structural configuration is not necessarily the competent coordination state for enzyme turnover. Oxygen ligation (from carboxylates, hydroxyl, water, or phosphate functionality) is common, although coordination by N-7 of guanosine is frequently observed in metal nucleotide structures in the solid state. In contrast to calcium-binding proteins, no general binding motifs have been clearly identified for magnesium sites in proteins.