Binding of hirudin to human alpha, beta and gamma-thrombin. A comparative kinetic and thermodynamic study.
J Mol Biol
; 225(1): 177-84, 1992 May 05.
Article
en En
| MEDLINE
| ID: mdl-1374801
ABSTRACT
Thermodynamic parameters for the binding of hirudin to human alpha, beta and gamma-thrombin have been determined between pH 5.0 and 9.0, and from 10 degrees C to 40 degrees C; kinetic data for the association and dissociation of the proteinase-inhibitor complex were obtained at pH 7.5 and 21 degrees C. These results have been analysed in parallel with the inhibitor-binding properties of human alpha, beta and gamma-thrombin for the bovine basic pancreatic trypsin inhibitor (Kunitz-type inhibitor; BPTI). For the purpose of an homogeneous comparison, values of the apparent association equilibrium constant for BPTI binding to human gamma-thrombin have been determined between pH 5.0 and 9.0, at 21 degrees C. The different binding behaviour of hirudin and BPTI with respect to human alpha, beta and gamma-thrombin has been related to the inferred stereochemistry of the proteinase-inhibitor contact regions. In particular, whereas the beta and gamma-loops play an appreciable role in the stabilization of the enzyme-hirudin complexes, they contribute to impairment of the adduct formation for the proteinase/BPTI system.
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Banco de datos:
MEDLINE
Asunto principal:
Trombina
/
Hirudinas
Límite:
Humans
Idioma:
En
Año:
1992
Tipo del documento:
Article