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J Biol Chem. 1990 Jun 15;265(17):10143-7.

Decorsin. A potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor from the leech Macrobdella decora.

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1
Department of Biomolecular Chemistry, Genentech, Inc., South San Francisco, California 94080.

Abstract

The discovery, purification, and characterization of decorsin, a protein isolated from the North American leech Macrobdella decora, are described. Decorsin acts as an antagonist of platelet glycoprotein IIb-IIIa (GPIIb-IIIa), and is a potent inhibitor of platelet aggregation. The protein was purified to apparent homogeneity from crude whole leech extracts by treatment with trifluoroacetic acid followed by GPIIb-IIIa affinity chromatography and C18 reverse-phase high performance liquid chromatography. Decorsin was also isolated from a solution of leech ingestate by treatment with trifluoroacetic acid followed by C18 reverse-phase high performance liquid chromatography. The primary sequence of decorsin indicates that the protein is 39 amino acids long and contains 6 cysteine and 6 proline residues, as well as the sequence Arg-Gly-Asp, (RGD), a proposed recognition site of many adhesion proteins. A molecular mass of 4379 was obtained by fast atom bombardment mass spectrometry and is consistent with the mass calculated from the observed sequence. Evidence for an N-3 isoform, lacking the first 3 amino-terminal residues is also presented. Both decorsin and the N-3 isoform inhibit GP IIb-IIIa binding to immobilized fibrinogen with an IC50 of approximately 1.5 nM. Human platelet aggregation induced by ADP is inhibited by decorsin with an IC50 of approximately 500 nM; complete inhibition was observed at less than or equal to 1 microM. Based on overall sequence homology, decorsin does not belong to the family of GPIIb-IIIa protein antagonists that is found in snake venoms (Dennis, M. S., Henzel, W. J., Pitti, R. M., Lipari, M. T., Napier, M. A., Deisher, T. A., Bunting, S., and Lazarus, R. A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2471-2475); however the carboxyl-terminal RGD-containing region from residues 27 to 38 of decorsin is approximately 60% homologous with the corresponding region of the snake venom proteins, suggesting that high affinity binding of these proteins to GPIIb-IIIa is defined by this epitope.

PMID:
2351655
[Indexed for MEDLINE]
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