A Structural Biochemistry Look at Blood Coagulation

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This structure shows thrombin complexed with hirugen and an active site inhibitor (PDB file 1A46). When thrombin is activated, its chain is cleaved into two pieces: the light chain (residues 1-15, green in the figure above) and the heavy chain (residues 16-247, red). This cleavage allows the protein to refold into a conformation in which the acitve site is open for business.

The space-filling structure is an active site inhibitor synthesized by Tulinsky et al. (J. Med. Chem. 42:1376-1383, 1999). Hirugen (blue chain) is a protein produced by leeches which binds to an exosite of thrombin and inhibits blood coagulation. This facilitates leech feeding.

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Structures of Coagulation Factors

The structures of many blood coagulation factors have been determined experimentally by X-ray crystallography or by NMR spectroscopy. The following is a survey of some of these structures.

• Tissue Factor (Factor III) is a member of the cytokine receptor superfamily.
• Tissue Factor + Factor VII form a complex.
• Von Willebrand Factor is an adhesive protein.
• Tissue Factor Pathway Inhibitor regulates the extrinsic pathway by inhibiting proteases.
• Protein C is a protease involved in down-regulating coagulation.
• Gamma-carboxy-glutamate residues are important for calcium binding in many coagulation factors.
• Thrombin is a key part of the coagulation pathway and is a target for drug design.
• Factor XIII is a transglutaminase which cross-links fibrin monomers to make the fibrin clot stronger.
• A Fibrin fragment has been crystallized.

Structures of Coagulation Factors

The structures of many blood coagulation factors have been determined experimentally by X-ray crystallography or by NMR spectroscopy. The following is a survey of some of these structures.

• Tissue Factor (Factor III) is a member of the cytokine receptor superfamily.
• Tissue Factor + Factor VII form a complex.
• Von Willebrand Factor is an adhesive protein.
• Tissue Factor Pathway Inhibitor regulates the extrinsic pathway by inhibiting proteases.
• Protein C is a protease involved in down-regulating coagulation.
• Gamma-carboxy-glutamate residues are important for calcium binding in many coagulation factors.
• Thrombin is a key part of the coagulation pathway and is a target for drug design.
• Factor XIII is a transglutaminase which cross-links fibrin monomers to make the fibrin clot stronger.
• A Fibrin fragment has been crystallized.