Enhancement of vitamin-K-dependent protein function by modification of the gamma-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, 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.
Nelsestuen
G L
GL
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul 55108, USA.
D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D005167:Factor VII / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D011485:Protein Binding; D011486:Protein C / Q000378:metabolism* / Q000627:therapeutic use*; D011498:Protein Precursors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D011486:Protein C; D011498:Protein Precursors; D011994:Recombinant Proteins; D015055:1-Carboxyglutamic Acid; D005167:Factor VII