Function
Antithrombin (AT) inactivates several enzymes of the coagulation cycle. AT is relatively inactive until it binds the heparan sidechains of the microvasculature.[1]
▪ α-AT contains 4 occupied glycosylation sites and is found in blood palsma.
▪ β-AT contains only 3 occupied glycosylation sites.
▪ AT-I refers to the absorption of thrombin to fibrin.
▪ AT-II and heparin interfere with the interaction of thrombin and fibrinogen.
▪ AT-III inactivates thrombin in plasma. For details see Student Projects for UMass Chemistry 423 Spring 2012-7.
▪ AT-IV becomes activated during blood coagulation.
See details for the antithrombin pentasaccharide complex in Molecular Playground/Antithrombin-Heparin.
Disease
AT deficiency diseases are: Acquired AT deficiency and Inherited AT deficiency. AT deficiency is involved in thrombosis and pulmonary embolism.
Relevance
AT activity is enhanced upon binding to the anticoagulant drug heparin.
Structural highlights
The binding of AT to the heparans or the heparin drug is to a core pentasaccharide. The binding induces conformational change of AT.
3D structures of antithrombin
Antithrombin 3D structures
- ↑ Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004 Sep;11(9):857-62. Epub 2004 Aug 15. PMID:15311269 doi:10.1038/nsmb811
