Ammodytagin, a heterodimeric metalloproteinase from Vipera ammodytes ammodytes venom with strong hemorrhagic activity

Toxicon. 2011 Nov;58(6-7):570-82. doi: 10.1016/j.toxicon.2011.09.004. Epub 2011 Sep 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Factor X / metabolism
  • Fibrinogen / metabolism
  • Hemorrhage / chemically induced*
  • Humans
  • Metalloproteases / chemistry
  • Metalloproteases / isolation & purification
  • Metalloproteases / toxicity*
  • Mice
  • Molecular Sequence Data
  • Plasminogen / metabolism
  • Prothrombin / metabolism
  • Rabbits
  • Rats
  • Viper Venoms / chemistry
  • Viper Venoms / enzymology
  • Viper Venoms / isolation & purification
  • Viper Venoms / toxicity*
  • Viperidae*


  • Viper Venoms
  • Prothrombin
  • Factor X
  • Fibrinogen
  • Plasminogen
  • Metalloproteases
  • ammodytagin, Vipera ammodytes ammodytes