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

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, γ-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. Copyright (C) 1999 Elsevier Science Inc.