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 Bothrop s jararaca, which is composed of a metalloprotease domain coupled to a disi ntegrin/cysteine-rich domain. It induces local haemorrhage owing to the pro teolytic digestion of the basement membrane of capillaries. Jararhagin also cleaves the alpha (2)beta (1) integrin on the surface of platelets, thereb y acting as a potent inhibitor of collagen-induced platelet aggregation. Cr ystals 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 80 00. Diffraction data have been obtained to a resolution of 2.8 Angstrom fro m a single frozen crystal, which belonged to space group P2(1)2(1)2(1) with unit-cell parameters a = 73.7, b = 100.3, c = 133.4 Angstrom. The asymmetr ic 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 met alloproteinase from the venom of the snake Agkistrodon acutus; attempts are under way to locate the remaining domains.