Enhancement of vitamin-K-dependent protein function by modification of the gamma-carboxyglutamic acid domain: studies of protein C and factor VII

Abstract

Vitamin-K-dependent proteins are found in both the pro- and anti-coagulation cascades, and their use in coagulation therapies is expanding rapidly. The vitamin-K-dependent, gamma-carboxyglutamic acid (Gla)-containing regions of proteins in this family are homologous and are responsible for membrane association. Site-directed mutations that enhance the membrane affinity of protein C, an anticoagulant, and of factor VII, a procoagulant, have been identified. These protein C and Factor VII mutants show enhanced activity in many assays, offering opportunities to study the role of membrane in blood clotting reactions and proteins that may have greater therapeutic value.