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TitleThe Prothrombin-Prothrombinase Interaction.
Journal, issue, pagesSubcell Biochem, Vol. 104, Page 409-423, Year 2024
Publish dateJul 4, 2024
AuthorsBosko M Stojanovski / Bassem M Mohammed / Enrico Di Cera /
PubMed AbstractThe hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with ...The hemostatic response to vascular injury entails a sequence of proteolytic events where several inactive zymogens of the trypsin family are converted to active proteases. The cascade starts with exposure of tissue factor from the damaged endothelium and culminates with conversion of prothrombin to thrombin in a reaction catalyzed by the prothrombinase complex composed of the enzyme factor Xa, cofactor Va, Ca, and phospholipids. This cofactor-dependent activation is paradigmatic of analogous reactions of the blood coagulation and complement cascades, which makes elucidation of its molecular mechanism of broad significance to the large class of trypsin-like zymogens to which prothrombin belongs. Because of its relevance as the most important reaction in the physiological response to vascular injury, as well as the main trigger of pathological thrombotic complications, the mechanism of prothrombin activation has been studied extensively. However, a molecular interpretation of this mechanism has become available only recently from important developments in structural biology. Here we review current knowledge on the prothrombin-prothrombinase interaction and outline future directions for the study of this key reaction of the coagulation cascade.
External linksSubcell Biochem / PubMed:38963494
MethodsEM (single particle)
Resolution6.47 Å
Structure data

42405

9cth

EMDB-42405, PDB-9cth:
Preliminary map of the Prothrombin-prothrombinase complex on nano discs
Method: EM (single particle) / Resolution: 6.47 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsBLOOD CLOTTING / Coagulation / Prothrombin / Prothrombinase / nanodisc / complex

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