{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T07:39:26Z","timestamp":1768721966649,"version":"3.49.0"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,11,21]],"date-time":"2003-11-21T00:00:00Z","timestamp":1069372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The venom of the South American snake <jats:italic>Bothrops jararaca<\/jats:italic> contains two serine proteinases, bothrombin and the platelet\u2010aggregating enzyme PA\u2010BJ, which share 66% sequence identity. Each of these proteinases possesses one of the two essential procoagulant functions of thrombin\u2014the clotting of fibrinogen and platelet aggregation. Thus, bothrombin clots fibrinogen but has no direct effect on platelets, unless in the presence of exogenous fibrinogen. PA\u2010BJ induces platelet aggregation by interacting with the protease\u2010activated platelet receptor without clotting fibrinogen. On the other hand, thrombin possesses two extended surfaces. One is composed of basic and hydrophobic residues (exosite I) and the other one of basic residues only (exosite II). These exosites are involved in the recognition of physiological macromolecular substrates. In order to identify the corresponding exosites in bothrombin and PA\u2010BJ and understand the molecular basis of the partition of the two procoagulant functions of thrombin among the two snake venom enzymes, we used molecular modeling to obtain models of their complexes with their natural substrates fibrinogen and a fragment of the protease\u2010activated platelet receptor, respectively. In analogy to thrombin, each of the enzymes presents two exosites. Nonetheless, the exosites contain a smaller proportion of basic residues than thrombin does (45\u201372%), reducing thus the functional diversity of the enzymes. In addition, the composition of exosite I is different in both enzymes. We identify those residues in exosite I that could contribute to the differences in specificity. Finally, allostery does not seem to mediate macromolecular substrate recognition by these enzymes. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jmr.644","type":"journal-article","created":{"date-parts":[[2004,2,9]],"date-time":"2004-02-09T18:31:08Z","timestamp":1076351468000},"page":"51-61","source":"Crossref","is-referenced-by-count":16,"title":["Identification of the substrate\u2010binding exosites of two snake venom serine proteinases: molecular basis for the partition of two essential functions of thrombin"],"prefix":"10.1002","volume":"17","author":[{"given":"R. C.","family":"Maroun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. M. 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