title: Vipera lebetina venom contains all types of snake venom metalloproteases.
abstract: Snake venoms contain four classes of metalloproteases that all have a typical zinc-chelating sequence (HEXXHGXXH). N-terminal sequences and internal sequences of different purified metalloproteases were determined using Edman sequencing and LC MS/MS technique. Oligonucleotides were designed and used as primers for cDNA cloning from Vipera lebetina venom gland cDNA library. We found that isoforms of fibrinolytic enzyme lebetase Le-4 and Le-3 are synthesized in different way: Le-4 is synthesized as P-I type metalloprotease, Le-3 is synthesized with disintegrin-like domain as P-II type protease and processed post-translationally. An endothelial cell apoptosis-inducing heterodimeric glycosylated metalloprotease, V. lebetina apoptosis-inducing protease (VLAIP), belongs to P-III type containing metalloprotease, disintegrin-like and cysteine-rich domains. All these enzymes hydrolyze the Aalpha-chain and more slowly the Bbeta-chain of fibrinogen. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes apoptosis. V. lebetina venom contains also P-IV type-specific coagulant factor X activator (VLFXA) that cleaves the Arg52-Ile53 bond in the heavy chain of human factor X. VLFXA is a glycoprotein composed of a heavy chain and two C-type lectin-like light chains linked by disulfide bonds. The heavy and light chains of VLFXA are synthesized from different genes.
authors.affiliation: National Institute of Chemical Physics and Biophysics, Tallinn, Estonia. siigur@kbfi.ee
authors.forename: J
authors.initials: J
authors.lastname: Siigur
authors.forename: K
authors.initials: K
authors.lastname: Tõnismagi
authors.forename: K
authors.initials: K
authors.lastname: Trummal
authors.forename: A
authors.initials: A
authors.lastname: Aaspõllu
authors.forename: M
authors.initials: M
authors.lastname: Samel
authors.forename: H
authors.initials: H
authors.lastname: Vija
authors.forename: J
authors.initials: J
authors.lastname: Subbi
authors.forename: N
authors.initials: N
authors.lastname: Kalkkinen
authors.forename: E
authors.initials: E
authors.lastname: Siigur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D045726:Metalloproteases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D020539:Sequence Analysis, Protein; D012910:Snake Venoms / Q000201:enzymology; D014470:Umbilical Cord; D014757:Viper Venoms / Q000201:enzymology*
chemical_list: D012910:Snake Venoms; D014757:Viper Venoms; D045726:Metalloproteases; D008666:Metalloendopeptidases; C069853:lebetase