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Interaction of site specific hirudin variants with α‐thrombin
Author(s) -
Dodt Johannes,
Köhler Stefanie,
Baici Antonio
Publication year - 1988
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(88)80803-2
Subject(s) - hirudin , thrombin , chemistry , discovery and development of direct thrombin inhibitors , biochemistry , biology , immunology , platelet
The kinetics of complex formation between recombinant hirudin or recombinant hirudin mutants with thrombin were analyzed. In order to elucidate the inhibitor's reactive site peptide bond predetermined amino acid substitutions were introduced at positions of basic amino acid residues by means of site‐directed mutagenesis of a hirudin gene. In comparison to recombinant hirudin ( K i = 19 pM) only those mutant inhibitors which were modified at amino acid position Lys 47 showed a higher K i value for their complexes with thrombin. The observed effects are mainly due to increased k off rate constants.