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Heparin-binding exosite of factor Xa.
1Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104, USA. rezaiear@slu.edu
Trends in Cardiovascular Medicine
|May 23, 2001
Summary
A specific site on factor Xa binds heparin when calcium is present, enhancing antithrombin inhibition. This site also binds factors Va and prothrombin, influencing coagulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Factor Xa is a key enzyme in the coagulation cascade.
- Its catalytic domain contains basic residues forming an exosite.
- This exosite's function is modulated by cofactor binding.
Purpose of the Study:
- To identify and characterize the exosite in factor Xa's catalytic domain.
- To understand the role of this exosite in heparin and cofactor binding.
- To elucidate how exosite interactions influence factor Xa's function.
Main Methods:
- Review of structural, mutagenesis, and kinetic data.
- Analysis of factor Xa's interaction with heparin and calcium.
- Investigation of factor Xa's role in the prothrombinase complex.
Main Results:
- Identified a specific exosite (Arg93, Lys96, Arg125, Arg165, Lys169, Lys236, Arg240) in factor Xa's catalytic domain.
- Demonstrated calcium-dependent heparin binding to this exosite.
- Showed that Arg165 and Lys169 are crucial for factor Va and prothrombin recognition.
Conclusions:
- The identified exosite is critical for factor Xa's interaction with heparin and subsequent antithrombin inhibition.
- This exosite plays a vital role in forming the prothrombinase complex by binding cofactors.
- Exosite interactions modulate factor Xa's specificity and function in plasma coagulation.