Antithrombin III – Thrombin interface (ATIII-IIa interface)

The Antithrombin III – Thrombin interface is a pivotal protein-protein interaction site responsible for the regulation of the blood coagulation cascade. Antithrombin III (ATIII), encoded by the SERPINC1 gene, is a serine protease inhibitor that neutralizes the activity of thrombin (Factor IIa) by forming a stable, inactive complex (UniProt P01008). This inhibitory process is naturally slow but is accelerated by more than 1,000-fold upon the binding of heparin or endogenous heparan sulfates to ATIII (StatPearls, Heparin). Pharmacologically, this interface is targeted by unfractionated heparin (UFH) and low molecular weight heparins (LMWH), which facilitate the formation of the ATIII-thrombin complex through an allosteric change in ATIII and a template mechanism (DrugBank DB01109). This interaction is essential for maintaining hemostasis and preventing pathological clot formation in conditions such as venous thromboembolism and myocardial infarction (PubMed, PMID: 21910471). Clinical management of this target requires careful monitoring of biomarkers like the activated partial thromboplastin time (aPTT) to balance anticoagulant efficacy against the risk of hemorrhage (StatPearls, Antithrombin III Deficiency).

Other names

Antithrombin-Thrombin complexATIII-FIIa interactionSERPINC1-F2 interfaceHeparin-Antithrombin-Thrombin ternary complex

Allosteric activation of Antithrombin III and template-mediated bridging of Antithrombin III to Thrombin