Interaction of site specific hirudin variants with alpha-thrombin |
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Authors: | J Dodt S K?hler A Baici |
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Institution: | Institut für Biochemie der Technischen Hochschule Darmstadt, FRG. |
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Abstract: | 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 (Ki = 19 pM) only those mutant inhibitors which were modified at amino acid position Lys47 showed a higher Ki value for their complexes with thrombin. The observed effects are mainly due to increased koff rate constants. |
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