The role of the C-terminal domain in the inhibitory functions of tissue factor pathway inhibitor

Tissue factor pathway inhibitor (TFPI) inhibits the activity of coagulation factors VIIa and Xa through Kunitz domains, thereby inhibiting the activit y of tissue factor. However, it has been shown that the C-terminal of this inhibitor is essential for the maximal anticoagulant activity of TFPI, We h ave investigated the endogenous ability of the C-terminal of TFPI to influe nce coagulation, A synthetic peptide corresponding to residues 254-265 with in the C-terminal of TFPI was prepared and shown to be capable of inhibitin g tissue factor pathway by preventing the activation of factor VII, Mutatio nal analysis of the peptide revealed the identity of the key lysine residue s. (C) 1999 Federation of European Biochemical Societies.