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The structural elements of hirudin which bind to the fibrinogen recognition site of thrombin are exclusively located within its acidic C‐terminal tail
Author(s) -
Chang Jui-Yoa,
Ngai Philip K.,
Rink Hans,
Dennis Stanley,
Schlaeppi Jean-Marc
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80573-2
Subject(s) - hirudin , thrombin , chemistry , fibrinogen , biochemistry , binding site , discovery and development of direct thrombin inhibitors , peptide , stereochemistry , antithrombin , biology , heparin , immunology , platelet
Six lysyl residues of human thrombin (Lys B21 , Lys B52 , Lys B65 , Lys B106 , Lys B107 and Lys B154 ) have been previously shown to participate in the binding site of hirudin, a thrombin‐specific inhibitor [(1989) J. Biol. Chem. 264, 7141‐7146]. In this report, we attempted to delineate the region of hirudin which binds to these basic amino acids of thrombin. Using the N‐terminal core domains ( r ‐Hir 1–43 and r ‐Hir 1–52 ) derived from recombinant hirudins and synthetic C‐terminal peptides (Hir 45–65 and Hir 52–65 ) ‐ all fragments form complexes with thrombin — we are able to demonstrate that the structural elements of hirudin which account for the shielding of these 6 lysyl residues are exclusively located within the acidic C‐terminal region. Since hirudin C‐terminal peptides were shown to bind to a non‐catalytic site of thrombin and inhibit its interaction with fibrinogen [(1987) FEBS Lett. 211, 10‐16], our data consequently imply that these 6 lysyl residues are constituents of the fibrinogen recognition site of thrombin.