What is heparin-binding domain?
What is heparin-binding domain?
Heparin-Binding Domain of AT. Heparin functions as an anticoagulant primarily through activation of AT-mediated inhibition of blood coagulation factors such as thrombin and factor Xa. Several steps are involved in the interaction of heparin with AT and serine proteases.
Which of the proteins provides a binding site for heparin?
The role of proteoglycans HGF is a heparin-binding protein. Mutation analyses have determined that a very few amino acids within the N terminus of the protein (Lys60, Lys62, Arg73, Arg76, Lys78) and a region from kringle 2 are primarily responsible for this characteristic (Mizuno et al., 1994; Zhou et al., 1999).
How does heparin bind to proteins?
Most proteins bind to heparin with a higher affinity than their fragments and form more stable complexes with heparin than with heparan sulfate. Lipoproteins and matrisome-associated proteins (e.g. growth factors and cytokines) bind to heparin with very high affinity.
Where does heparin bind?
Heparin binds to AT through a high-affinity pentasaccharide, which is present on about a third of heparin molecules. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and AT, whereas binding to the enzyme is not required for inhibition of factor Xa.
Which amino acid residues of clotting proteins are likely to interact with heparin?
Arginine and lysine are the most frequent residues in heparin- and HS-binding proteins. Although both amino acids have a positive charge at physiological pH, arginine binds heparin ≈2.5× more tightly. Arginine forms more stable hydrogen bonds as well as stronger electrostatic interactions with sulfo groups.
What is the biological function for heparin?
The major and best known function of heparin is anticoagulation of blood. Heparin binds toserine protease inhibitor antithrombin III (AT) which results in activation of AT. The activated AT blocks thrombin and inactivates factors Xa and IIa which are responsible for blood coagulation.
Can heparin break up clots?
Heparin will not dissolve blood clots that have already formed, but it may prevent the clots from becoming larger and causing more serious problems.
Which clotting factors are affected by heparin?
By binding to antithrombin (AT), a glycoprotein synthesized in the liver and vascular endothelium, heparin markedly enhances the rate of AT-mediated inactivation of clotting factors (factors IX, X, XI, and XII and thrombin).
