Contribution of Pro212-Ile276 sequence of human protein C to its anticoagulant and profibrinolytic activity

Thrombosis Research
I FijalkowskaC S Cierniewski

Abstract

Activated protein C exhibits strong anticoagulant and profibrinolytic properties. The Pro212-Ile276 fragment of a heavy chain of the protein molecule is located in the nearest neighborhood of the catalytic domain. It was found that polyclonal antibodies against this fragment recognize the sequence in the native molecule. To determine the contribution of the fragment in the anticoagulant and profibrinolytic activities of the enzyme, competitive inhibition analyses were performed. We found that amidolytic activity of the enzyme was inhibited by the recombinant Pro212-Ile276 fragment in a dose-dependent manner. Also, the fusion protein prolonged the time of clot lysis in a micro-clot lysis assay. The presence of the recombinant protein fragment did not influence the reaction of activated protein C with factor Va, neither the reaction of the enzyme with its specific inhibitor. We conclude, that Pro212-Ile276 region of protein C can not be identified with the binding pocket of the enzyme, but might be a binding site for small, low molecular weight substrates like chromogenic substrate.

References

Jan 1, 1977·Annual Review of Biochemistry·J Kraut
Oct 15, 1991·Thrombosis Research·M L LewisK L Damron
Apr 1, 1994·Protein Science : a Publication of the Protein Society·C L FisherJ H Griffin
Dec 1, 1993·Journal of Protein Chemistry·H C Whinna, F C Church
Sep 1, 1993·Protein Science : a Publication of the Protein Society·R M MestersJ H Griffin
Feb 13, 1993·Biochimica Et Biophysica Acta·I FijalkowskaC S Cierniewski

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