General features of the heparin-binding serpins antithrombin, heparin cofactor II and protein C inhibitor.
The blood plasma serine proteinase inhibitors (serpins) are glycoproteins whose activities are involved in many important homeostatic reactions. The heparin-dependent plasma serpins, antithrombin, heparin cofactor II and protein C inhibitor, regulate the proteinases of blood coagulation. Heparin and some other glycosaminoglycans increase the rate of proteinase inhibition by these three plasma serpins. Proteinases recognize a specific peptide, termed the reactive site, near the carboxyl-terminus of serpins (for antithrombin and protein C inhibitor this is Arg-Ser and for heparin cofactor II this is Leu-Ser). Additionally, these three serpins contain unique structural elements that confer glycosaminoglycan binding activities. The therapeutic anticoagulant action of the glycosaminoglycan heparin is believed to depend partially on heparin-accelerated inhibition of proteinases by antithrombin. The physiological importance of specific proteoglycans has been attributed to their recognition of these serpins and their biological 'activation' of these proteinase inhibitors.
Pratt
C W
CW
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599.
Church
F C
FC
D000595:Amino Acid Sequence; D000991:Antithrombins / Q000378:metabolism*; D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D006025:Glycosaminoglycans / Q000378:metabolism; D006487:Hemostasis; D006493:Heparin / Q000378:metabolism*; D015844:Heparin Cofactor II / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011485:Protein Binding; D018046:Protein C Inhibitor; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
D000991:Antithrombins; D001779:Blood Coagulation Factors; D006025:Glycosaminoglycans; D015849:Plasminogen Inactivators; D018046:Protein C Inhibitor; D015843:Serpins; D015844:Heparin Cofactor II; D006493:Heparin; D013917:Thrombin