The functional domain of hirudin, a thrombin‐specific inhibitor

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Abstract
Hirudin is a thrombin-specific of M r 8000 (65 amino acid residues). Native hirudin contains 3 disulfide linkages within the first 39 amino-terminal residues, and highly C-terminal segment which is freely accessible to enzyme digestion by both endo- and exo-peptidases. Removal of the acidic C-terminal amino acids of native hirudin by both chemical and enzymatic methods resulted in a concomitant loss of hirudin inhibition activity. It is concluded that this acidic C-terminal segment of hirudin is essential for hirudin—thrombin interaction. The implication of the hirudin—thrombin interaction for the enzymatic specificity of thrombin is also discussed.