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Published on: February 17, 2017
Heparanase Activates Antithrombin through the Binding to Its Heparin Binding Site
Nataliya Bohdan1, Salvador Espín1, Sonia Águila1
1Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
Heparanase directly interacts with and activates antithrombin, the primary anticoagulant, through a non-enzymatic mechanism. This finding reveals a novel role for heparanase in regulating blood coagulation and anticoagulation processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Hemostasis
Background:
- Heparanase is an endoglycosidase involved in tissue repair and metastasis.
- It can influence the hemostatic system non-enzymatically, promoting a procoagulant state.
- Its interaction with anticoagulants like antithrombin is not fully understood.
Purpose of the Study:
- To investigate the effect of heparanase on heparin's activation of antithrombin.
- To determine if heparanase directly interacts with antithrombin.
- To elucidate the mechanism of heparanase-antithrombin interaction and its functional consequences.
Main Methods:
- Studied the interaction between heparanase and antithrombin using biochemical assays.
- Utilized antithrombin mutants to identify the binding site.
- Employed intrinsic fluorescence analysis to assess conformational changes.
Main Results:
- Heparanase, but not proheparanase, directly interacted with antithrombin non-covalently.
- This interaction activated antithrombin, enhancing Factor Xa inhibition, suggesting allosteric activation.
- Heparanase bound to the heparin-binding site of antithrombin, confirmed by mutant studies.
Conclusions:
- Heparanase exerts a non-enzymatic function by interacting with and activating antithrombin's inhibitory function.
- This interaction may play a role in regulating anticoagulation under physiological conditions.
- Heparanase's interaction with antithrombin is distinct from its enzymatic activity and involves its heparin-binding site.
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