Title : Occupancy of anion binding exosite 2 on thrombin determines Ca2+ dependence of protein C activation.

Pub. Date : 1994 Apr 22

PMID : 8163479






5 Functional Relationships(s)
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Compound Name
Protein Name
Organism
1 Thrombomodulin (TM) binds thrombin to form a complex that activates the plasma anticoagulant zymogen protein C. TM is an integral membrane glycoprotein that contains a chondroitin sulfate moiety. Chondroitin Sulfates coagulation factor II, thrombin Homo sapiens
2 Interaction with thrombin involves both the protein component of TM, specifically the growth factor-like repeats 4-6 (TM 4-6), and chondroitin sulfate. Chondroitin Sulfates coagulation factor II, thrombin Homo sapiens
3 Removal of chondroitin sulfate decreases the affinity for thrombin approximately 10-fold and shifts the Ca2+ dependence of protein C activation from simple saturation at > or = 500 microM Ca2+ to a distinct optimum at approximately 100 microM Ca2+. Chondroitin Sulfates coagulation factor II, thrombin Homo sapiens
4 At 0.27 mM Ca2+, TM containing chondroitin sulfate binds thrombin (Kd(app) = 0.3 nM) approximately 45 times tighter than meizothrombin des-fragment 1 (Kd(app) = 14 nM). Chondroitin Sulfates coagulation factor II, thrombin Homo sapiens
5 These studies suggest that occupancy of anion binding exosite 2 by either chondroitin sulfate or fragment 2 alters thrombin conformation resulting in the altered Ca2+ dependence of protein C activation. Chondroitin Sulfates coagulation factor II, thrombin Homo sapiens