Antithrombin: Difference between revisions
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{{ | {{STRUCTURE_13evj| PDB=3evj | SIZE=400| SCENE= |right|CAPTION=Antithrombin (beige) complex with thrombin heavy chain (pink), light chain (green) and heparin polysaccharide, [[1tb6]] }} | ||
'''Antithrombin''' (AT) inactivates several enzymes of the coagulation cycle. 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; AT-IV becomes activated during blood coagulation. See details for the antithrombin pentasaccharide complex in [[Molecular Playground/Antithrombin-Heparin]]. | '''Antithrombin''' (AT) inactivates several enzymes of the coagulation cycle. 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; AT-IV becomes activated during blood coagulation. See details for the antithrombin pentasaccharide complex in [[Molecular Playground/Antithrombin-Heparin]]. | ||
== Function == | |||
'''Antithrombin''' (AT) inactivates several enzymes of the coagulation cycle. AT is relatively inactive until it binds the heparan sidechains of the microvasculature.<br /> | |||
▪ α-AT contains 4 occupied glycosylation sites and is found in blood palsma.<br /> | |||
▪ β-AT contains only 3 occupied glycosylation sites.<br /> | |||
▪ AT-I refers to the absorption of thrombin to fibrin.<br /> | |||
▪ AT-II and heparin interfere with the interaction of thrombin and fibrinogen.<br /> | |||
▪ AT-III inactivates thrombin in plasma.<br /> | |||
▪ AT-IV becomes activated during blood coagulation.<br /> | |||
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== | ==3D structures of antithrombin== | ||
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*Antithrombin binary complexes | *Antithrombin binary complexes | ||
**[[1azx]], [[1nq9]], [[3evj]] | **[[1azx]], [[1nq9]], [[3evj]], [[1e03]] – hAT III + heparin pentasaccharide | ||
**[[1dzh]] - hAT-III (mutant) + fluorescein | **[[1dzh]] - hAT-III (mutant) + fluorescein | ||