Publisher Summary This chapter discusses the ways in which calcium is bound to a protein as well as the role of calcium in protein function. Proteins that contain γ-carboxyglutamic acid (Gla) are discussed as an example of proteins that bind calcium mainly by bidentate chelation. Prothrombin is the prototypical Gla-containing plasma protein, especially with regard to structural characteristics and calcium- and phospholipid-binding properties. Lectins are proteins that have no known enzymatic activity, but exhibit numerous biological activities that are related to their ability to bind carbohydrates in the presence of divalent cations. The proposed roles for calcium and the postulated calcium-binding sites are based on homology with concanavalin A (Con A). A variety of enzymes that catalyze the hydrolysis of ester, phosphodiester, and peptide bonds bind calcium ions. The calcium-binding hydrolytic enzymes include many hydrolytic enzymes, but mechanistic and crystallographic data are available only for phospholipase A2, staphylococcal nuclease, thermolysin, trypsin, and chymotrypsin. The vitamin D-dependent calcium-binding protein structure indicates that intracellular calcium-modulated proteins may utilize other structures for calcium-binding.