Antistasin, an inhibitor of coagulation and metastasis, binds to sulfatide (Gal(3-SO4) beta 1-1Cer) and has a sequence homology with other proteins that bind sulfated glycoconjugates.
Antistasin, a 15-kDa salivary protein from the Mexican leech Haementeria officinalis, inhibits both blood coagulation and the metastasis of tumors (Tuszynski, G. P., Gasic, T. B., and Gasic, G. J. (1987) J. Biol. Chem. 262, 9718-9723). Antistasin binds to heparin-agarose, suggesting the protein interacts with sulfated glycoconjugates. The specificity of the interaction between antistasin and heparin was tested by measuring the binding of antistasin to various lipids and by comparing the ability of several charged glycoconjugates to inhibit binding. Of the lipids tested, antistasin binds with high affinity only to sulfatide (Gal(3-SO4)beta 1-1Cer) and does not bind to comparable levels of phospholipids, neutral glycosphingolipids, gangliosides, or cholesterol-3-SO4. The binding of antistasin to sulfatide is inhibited by dextran sulfate, fucoidan, and heparin, with I50 values of 1.5, 9.2, and 16 micrograms/ml, respectively. Comparable levels of chondroitin sulfates A, B, C, keratan sulfate, or hyaluronic acid do not inhibit binding. Comparisons of the amino acid sequences of antistasin and other sulfatide or heparin-binding proteins revealed a region of homology, based around the sequence Cys-Ser-Val-Thr-Cys-Gly-X-Gly-X-X-X-Arg-X-Arg, which may be a sulfated glycoconjugate binding domain. In addition, homologies were found with the alternate complement pathway protein properdin and coat proteins from malaria circumsporozoites and Herpes simplex I.
Holt
G D
GD
Laboratory of Structural Biology, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Krivan
H C
HC
Gasic
G J
GJ
Ginsburg
V
V
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D007447:Invertebrate Hormones / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000494:pharmacology; D011485:Protein Binding; D012471:Salivary Proteins and Peptides / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013433:Sulfoglycosphingolipids / Q000378:metabolism*
D000925:Anticoagulants; D000970:Antineoplastic Agents; D007447:Invertebrate Hormones; D011134:Polysaccharides; D012471:Salivary Proteins and Peptides; D013433:Sulfoglycosphingolipids; C053155:antistasin