Antithrombin

<StructureSection load='3evj' size='340' side='right' caption='Glycosylated human antithrombin III complex with heparin (PDB code 2ohy)' scene=>

Function

Antithrombin (AT) inactivates several enzymes of the coagulation cycle. AT is relatively inactive until it binds the heparan sidechains of the microvasculature.
▪ 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.

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

Updated on 03-November-2015

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• Antithrombin
  • 1att – AT-III – bovine
  • 1ant, 2ant – hAT – human
  • 1e05 - hα-AT-III
  • 1e04 – hβ-AT-III
  • 1ath, 2znh, 4eb1 – hAT-III
  • 1dzg, 1oyh, 1t1f, 2beh, 2b4x, 2hij - hAT-III (mutant)
• Antithrombin binary complexes
  • 1azx, 1nq9, 3evj, 1e03 – hAT III + heparin pentasaccharide
  • 1dzh - hAT-III (mutant) + fluorescein
  • 2gd4 - hAT-III (mutant) + coagulation factor X
  • 1br8, 1jvq, 1lk6, 1r1l – hAT-III + peptide
• Antithrombin ternary complexes
  • 1sr5 - hAT-III + prothrombin + heparin heptasaccharide
  • 1tb6 - hAT-III (mutant) + thrombin + heparin polysaccharide
  • 2b5t - AT-III (mutant) + thrombin (mutant) + heparin polysaccharide
  • 3kcg - hAT-III (mutant) + coagulation factor IXa + heparin pentasaccharide

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky