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Science 24 June 1994:
Vol. 264. no. 5167, pp. 1944 - 1947
DOI: 10.1126/science.8009227
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Articles

Science, Vol 264, Issue 5167, 1944-1947
Copyright © 1994 by American Association for the Advancement of Science

articles

Structure of the RGD protein decorsin: conserved motif and distinct function in leech proteins that affect blood clotting

AM Krezel, G Wagner, J Seymour-Ulmer, and RA Lazarus

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.

The structure of the leech protein decorsin, a potent 39-residue antagonist of glycoprotein IIb-IIIa and inhibitor of platelet aggregation, was determined by nuclear magnetic resonance. In contrast to other disintegrins, the Arg-Gly-Asp (RGD)-containing region of decorsin is well defined. The three-dimensional structure of decorsin is similar to that of hirudin, an anticoagulant leech protein that potently inhibits thrombin. Amino acid sequence comparisons suggest that ornatin, another glycoprotein IIb-IIIa antagonist, and antistasin, a potent Factor Xa inhibitor and anticoagulant found in leeches, share the same structural motif. Although decorsin, hirudin, and antistasin all affect the blood clotting process and appear similar in structure, their mechanisms of action and epitopes important for binding to their respective targets are distinct.


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