Souza D H, Selistre-de-Araujo H S, Moura-da-Silva A M, Della-Casa M S, Oliva G, Garratt R C
Departamento de Física e Informática, Instituto de Física de São Carlos, Universidade de São Paulo, Brazil.
Acta Crystallogr D Biol Crystallogr. 2001 Aug;57(Pt 8):1135-7. doi: 10.1107/s090744490100614x. Epub 2001 Jul 23.
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 haemorrhage owing to the proteolytic digestion of the basement membrane of capillaries. Jararhagin also cleaves the alpha(2)beta(1) 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 A from 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 A. 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.
矛头蝮蛇毒金属蛋白酶是一种从矛头蝮蛇毒液中分离出的有毒蛋白质，它由一个金属蛋白酶结构域与一个去整合素/富含半胱氨酸结构域相连组成。由于它对毛细血管基底膜的蛋白水解作用，可导致局部出血。矛头蝮蛇毒金属蛋白酶还能裂解血小板表面的α(2)β(1)整合素，因此它是胶原诱导的血小板聚集的有效抑制剂。通过气相扩散技术，在273K下，于200mM醋酸钠、100mM二甲胂酸钠缓冲液（pH6.5）和30%聚乙二醇8000中获得了矛头蝮蛇毒金属蛋白酶的晶体。从一个属于空间群P2(1)2(1)2(1)、晶胞参数a = 73.7、b = 100.3、c = 133.4 Å的单个冷冻晶体中获得了分辨率为2.8 Å的衍射数据。不对称单元包含两个矛头蝮蛇毒金属蛋白酶分子，溶剂含量为45%。使用基于来自五步蛇毒液的出血性锌金属蛋白酶——尖吻蝮溶血素晶体结构的同源构建模型，获得了分子置换解；目前正在尝试定位其余结构域。
