ABSTRACT
Ca2+ is preferentially coordinated by oxygens, usually from aspartic acid and glutamic acid side chains, as well as the carbonyl oxygens of the peptide backbone. The number of ligand atoms bound to Ca2+ can vary from five to eight, but the most common number is seven. In addition to oxygen ligands contributed from the protein, water molecules often function as ligands. Though usually only one or two ligands are contributed by water, there are cases of Ca2+ being coordinated by three or even four water ligands, as is the case for proteinase K [7]. Ca2+ binding constants can vary up to seven orders of magnitude from weak binders such as certain EGF domains (logK a ~ 3) to strong binders such as thermolysin or subtilisin (logK a ~ 10). Surprisingly, however, in a recent survey of Ca2+-binding proteins, absolutely no correlation was found between Ca2+ affinity and many properties of the Ca2+ coordi nation sphere, such as net ligand charge, number of water molecules in the coordina tion sphere, number of protein ligands, or number of backbone protein ligands [3] (Fig. 1). Instead, it was concluded that subtler forces determine Ca2+ affinity. These included polypeptide strain, surface charges near the binding site, and the amount of conformational change induced upon Ca2+ binding.
