Calcium Ion Binding to Vitamin K-dependent Clotting Factors

Calcium ions have long been recognized as necessary for clot formation. It was 1972 that γ-carboxyglutamic acid (Gla) was discovered in bovine prothrombin. In two decades, the relationship of the Gla residues in vitamin K-dependent clotting factors and calcium binding properties has been extensively studied by many investigators. Recent advances in molecular biology and crystallographic study brought us to construct the experiments for understanding the role of the individual Gla residues in their calcium ion-dependent functions. In this report, the very recent studies about the Gla-dependent and independent calcium binding properties of vitamin K-dependent clotting factors were reviewed.