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Thromb Haemost 1999; 82(05): 1469-1473
DOI: 10.1055/s-0037-1614857
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A New Factor Xa Inhibitor (Lefaxin) from the Haementeria depressa Leech

Fernanda Faria
1   From Laboratorio de Fisiopatologia, Instituto Butantan; São-Paulo, Brasil
,
Eva Maria A. Kelen
1   From Laboratorio de Fisiopatologia, Instituto Butantan; São-Paulo, Brasil
,
Claudio A. M. Sampaio
2   Departamento de Bioquímica e Biologia Molecular, Universidade Federal de São Paulo (UNIFESP-EPM) São Paulo, Brasil
,
Cassian Bon
3   Unité des Venins, Institut Pasteur, Paris, France
,
Nathalie Duval   *
3   Unité des Venins, Institut Pasteur, Paris, France
,
Ana Marisa Chudzinski-Tavassi
1   From Laboratorio de Fisiopatologia, Instituto Butantan; São-Paulo, Brasil
› Author Affiliations
Further Information

Publication History

Received 15 December 1998

Accepted after resubmission 07 June 1999

Publication Date:
09 December 2017 (online)

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Summary

The salivary complex of the leech Haementeria depressa produces potent anticoagulant components. Among them, a protein named lefaxin inhibits factor Xa (FXa). Lefaxin was purified to homogeneity from dissected salivary complexes by gel filtration in Sephadex G-150 followed by two ion exchange chromatography steps in Mono-Q. Inhibition of FXa by lefaxin was demonstrated by the inhibition of its amidolytic activity, measured with chromogenic substrate S-2765 (apparent KI of 4 nM), and of its ability to inhibit thrombin generation in the prothrombinase complex (EC50 of 40 nM). Lefaxin has a molecular weight of 30 kDa and an isoelectric point of 5.7. It is made of a polypeptide chain whose N-terminal sequence shows no similarity with that of other FXa inhibitors (antistasin and ghilianten) isolated from leech saliva. On the other hand, the N-terminal sequence of lefaxin presents significant sequence similarity with nitric oxide carrier proteins myohemerythrin from the annelid Nereis diversicolor and prolixin S from the tick Rhodnius prolixus. Interestingly, prolixin S also proved to be an anticoagulant protein acting on FXa.

Keywords

Leeches - FXa inhibitor - Haementeria depressa

* Present address: Dr. N. Duval, Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, Paris, France


 

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