Bothrops asper hemorrhagic proteinases

This chapter examines the structural chemistry and the biological aspects of bothrops asper hemorrhagic (BaH1) proteinases. BaH1 hydrolyzes Azocoll and BaP1 has proteolytic activity on hide powder azure, casein, fibrinogen, fibronectin, collagen type I, collagen type IV and laminin. Upon incubation with fibrinogen, BaPl causes rapid degradation of the Aa chain and, more slowly, of the β chain, whereas no degradation of the ã chain is observed. BaH4 has proteolytic activity on casein, hide powder azure, and fibrin, and on fibronectin, laminin and type IV collagen. Hydrolysis of hide powder azure by BaPl is optimal at pH 8.0. Both BaHl and BaPl are thermolabile, losing their activity after incubation at 60°C. BaH1, BaH4 and BaP1 are inhibited by chelating agents, but not by soybean trypsin inhibitor, PMSF, pepstatin A or phosphoramidon. In addition, BaH1 is inhibited by NtAH and BaSAH, antihemorrhagic factors isolated from the serum of the snakes Natrix tessellata and Bothrops asper, respectively. BaPl and BaH4 are inhibited by a protein purified from the serum of Didelphis albiventris, and both enzymatic and hemorrhagic activities of BaPl are inhibited by the peptidomimetic hydroxamate matrix metalloproteinase inhibitor batimastat.