Triabin, a highly potent exosite inhibitor of thrombin.
Triabin, a new thrombin inhibitor, has been purified from the saliva of Triatoma pallidipennis, a blood-sucking triatomine bug. It forms a noncovalent complex with thrombin at a molar ratio of 1:1, inhibits thrombin-induced platelet aggregation, and prolongs thrombin clotting time and activated partial thromboplastin time. However, it only minimally suppresses the amidolytic activity of thrombin, as measured by a chromogenic peptide substrate assay. It completely blocks trypsin-catalyzed cleavage of thrombin, probably via protection of the anion-binding exosite and inhibits the effect of thrombomodulin on thrombin in a dose-dependent fashion. These results indicate that the inhibitor is directed toward the anion-binding exosite of thrombin. The protein was partially sequenced and the information used to isolate cDNA clones from a T. pallidipennis salivary gland library. Four slightly polymorphic variants coding for mature proteins of 142 amino acids preceded by a putative leader sequence were obtained. The recombinant protein expressed in the periplasmic space of Escherichia coli has a biological activity similar to that of salivary triabin, as tested in a thrombin-induced platelet aggregation assay. In addition, recombinant triabin inhibits thrombin-catalyzed hydrolysis of fibrinogen with a Ki of about 3 pM.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D019476:Insect Proteins; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012463:Saliva / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D014224:Triatoma; D014357:Trypsin / Q000378:metabolism
D017931:DNA Primers; D018076:DNA, Complementary; D019476:Insect Proteins; D010975:Platelet Aggregation Inhibitors; D012471:Salivary Proteins and Peptides; D015842:Serine Proteinase Inhibitors; D018180:Thrombomodulin; C097048:triabin; D014357:Trypsin; D013917:Thrombin