Crystallization and preliminary X-ray analysis of jararhagin, a metalloproteinase/disintegrin from Bothrops jararaca snake venom.

Jararhagin is a toxic protein, isolated from the venom of the snake Bothrops jararaca, which is composed of a metalloprotease domain coupled to a disintegrin/cysteine-rich domain. It induces local haemorrh age owing to the proteolytic digestion of the basement membrane of capillaries. Jararhagin also cleaves the α₂β₁ integrin on the surface of platelets, thereby acting as a potent inhibitor of collagen-induced platelet aggregation. Crystals of jararhagin were obtained by the vapour-diffusion technique at 273 K in 200 mM sodium acetate, 100 mM cacodylate buffer pH 6.5 and 30% PEG 8000. Diffraction data have been obtained to a resolution of 2.8 Å from a single frozen crystal, which belonged to space group P2₁2₁2₁ with unit-cell parameters a = 73.7, b = 100.3, c = 133.4 Å. The asymmetric unit contains two jararhagin molecules and has a solvent content of 45 %. A molecular-replacement solution has been obtained using a homology-built model based on the crystal structure of acutolysin, a haemorrhagic zinc metalloproteinase from the venom of the snake Agkistrodon acutus; attempts are under way to locate the remaining domains. [ABSTRACT FROM AUTHOR]