|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
WR Church, FH Bhushan, KG Mann and EG Bovill
Department of Biochemistry, College of Medicine, University of Vermont,
Burlington 05405.
Vitamin K deficiency or administration of vitamin K antagonists results in
the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin
K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K-
dependent proteins at a determinant that includes the first two residues of
gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated
prothrombin and protein C in the presence of EDTA but binding is inhibited
by the divalent metal ions, calcium, magnesium, and manganese. By contrast,
des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in
the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a
conserved antigenic site containing gamma-carboxyglutamic acid that in the
presence of divalent metal ion undergoes a conformational transition. This
ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein
C in the presence of calcium ion allowed the development of an immunoassay
for these proteins in plasma. Prothrombin and protein C from stably
anticoagulated individuals receiving warfarin were characterized by their
ability to bind antibody H-11 in the presence of calcium ion. Binding of
prothrombin and protein C to antibody H-11 in the presence of calcium
correlated temporally with warfarin administration. The inability of
calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and
protein C in plasma suggests that the circulating forms of both proteins
following warfarin administration cannot undergo the metal ion-dependent
conformational transition that includes sequence residues 1 through 12.
This article has been cited by other articles:
| |||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
