title: Ammodytagin, a heterodimeric metalloproteinase from Vipera ammodytes ammodytes venom with strong hemorrhagic activity.
abstract: Ammodytagin, a hemorrhagic Zn(2+)-dependent metalloproteinase from Vipera ammodytes ammodytes (Vaa) venom, is a glycosylated heterodimer of 108 kDa, as determined by MALDI mass spectrometry. Partial amino acid sequencing by Edman degradation and MS/MS analysis identified sequences belonging to metalloproteinase, disintegrin-like and cysteine-rich domains, which in addition to its heterodimeric nature allows classification into the P-IIIc group of snake venom metalloproteinases (SVMPs). Only few members of that group have been described so far. Ammodytagin possesses potent azocaseinolytic activity which can be inhibited by Na(2)EDTA, Zn(2+) and DTT. It cleaves insulin B-chain, hydrolysing it at positions Gln(4)-His(5), His(10)-Leu(11) and Tyr(16)-Leu(17). Furthermore, ammodytagin acts as a strong hemorrhagin in both rats and mice. Investigation of a substrate specificity revealed that the hemorrhagic activity of the novel SVMP might be the result of its involvement in cleavage of basal membrane components and depletion of fibrinogen, prothrombin and factor X in blood circulation. Finally, antiserum raised against ammodytagin was able to completely neutralise the hemorrhagic activity of the whole venom, suggesting it might be one of the key molecules towards which effective Vaa specific antivenom should be directed.
authors.affiliation: Research and Development Department, Institute of Immunology, Inc, Rockefellerova 10, 10 000 Zagreb, Croatia. tkurtovic@imz.hr
authors.forename: Tihana
authors.initials: T
authors.lastname: Kurtović
authors.forename: Marija
authors.initials: M
authors.lastname: Brgles
authors.forename: Adrijana
authors.initials: A
authors.lastname: Leonardi
authors.forename: Maja Lang
authors.initials: ML
authors.lastname: Balija
authors.forename: Igor
authors.initials: I
authors.lastname: Križaj
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.forename: Martina
authors.initials: M
authors.lastname: Marchetti-Deschmann
authors.forename: Beata
authors.initials: B
authors.lastname: Halassy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005170:Factor X / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D045726:Metalloproteases / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014757:Viper Venoms / Q000737:chemistry / Q000201:enzymology / Q000302:isolation & purification / Q000633:toxicity*; D017819:Viperidae
chemical_list: D014757:Viper Venoms; D011516:Prothrombin; D005170:Factor X; D005340:Fibrinogen; D010958:Plasminogen; D045726:Metalloproteases; C569457:ammodytagin, Vipera ammodytes ammodytes