tailieunhanh - Báo cáo khoa học: The first phospholipase inhibitor from the serum of Vipera ammodytes ammodytes

Ammodytoxins are neurotoxic secretory phospholipase A2molecules, some of the most toxic components of the long-nosed viper (Vipera ammo-dytes ammodytes) venom. Envenomation by this and by closely related vipers is quite frequent in southern parts of Europe and serotherapy is used in the most severe cases. | ỊFEBS Journal The first phospholipase inhibitor from the serum of Vipera ammodytes ammodytes I 1 1 I I IX V. v1 l-x . I-S v I V1 I- 2 I I IX v 1 Jernej Sribar Lidija Kovacic Petra Draskovic Grazyna Faure and Igor KriZaj 1 Department of Molecular and BiomedicalSciences Jozef Stefan Institute Ljubljana Slovenia 2 Unite d Immunologie Structurale Institut Pasteur Paris France Keywords ammodytoxin inhibitor secretory phospholipase A2 snake serum Vipera ammodytes ammodytes Correspondence I. Krizaj Department of Molecular and BiomedicalSciences Jozef Stefan Institute Jamova 39 SI-1000 Ljubljana Slovenia Fax 386 1477 3984 Tel 386 1477 3626 E-mail Received 26 June 2007 revised 2 October 2007 accepted 4 October 2007 doi Ammodytoxins are neurotoxic secretory phospholipase A2 molecules some of the most toxic components of the long-nosed viper Vipera ammo-dytes ammodytes venom. Envenomation by this and by closely related vipers is quite frequent in southern parts of Europe and serotherapy is used in the most severe cases. Because of occasional complications alternative medical treatment of envenomation is needed. In the present study ammo-dytoxin inhibitor was purified from the serum of V. a. ammodytes using two affinity procedures and a gel exclusion chromatography step. The ammodytoxin inhibitor from V. a. ammodytes serum consists of 23- and 25-kDa glycoproteins that form an oligomer probably a tetramer of about 100 kDa. N-terminal sequencing and immunological analysis revealed that both types of subunit are very similar to y-type secretory phospholipase A2 inhibitors. The ammodytoxin inhibitor from V. a. ammodytes serum is a potent inhibitor of phospholipase activity and hence probably also the neurotoxicity of ammodytoxins. Discovery of the novel natural inhibitor of these potent secretory phospholipase A2 toxins opens up prospects for the development of new types of small peptide inhibitors for use in regulating the .