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.
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599.
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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