Crystallization and Preliminary X-ray Analysis of Vipoxin, a Complex between a Toxic Phospholipase A2 and its Natural Polypeptide Inhibitor

Crystal structure of vipoxin at 2.0 Å: an example of regulation of a toxic function generated by molecular evolution

“…The ability to produce substrates for the generation of inflammatory lipid mediators in the process of tissue injury and rheumatoid arthritis [2]makes this specific class of phospholipases of medical and pharmaceutical interest. Structure‐based drug design for the development of potent and specific inhibitors for these enzymes has led to the characterization and structural analysis of several PLA 2 s and their complexes with substrate analogues [3–11].…”

X-ray structure at 1.76 Å resolution of a polypeptide phospholipase A2 Inhibitor 1 1 Edited by R. Huber

“…The data set collected could not be used further for the determination of the structure of vipoxin (Y. Devedjiev, M. T. Stubbs & R. Huber, unpublished results). Betzel et al (1993) reported preparation of crystals of vipoxin similar to ours using a different protocol.…”

“…This proves the suggestion that the inhibitor originates from an ancestral PLA and that it is a product of a divergent evolution. To the best of our knowledge, the structural aspects of the action of a polypeptide PLA 2 inhibitor from snake venom have not been investigated yet, although preliminary X-ray investigations for crystals of the neurotoxic complexes, crotoxin (Achari et al, 1985) and vipoxin (Betzel et al, 1993), suitable for high resolution X-ray diffraction analysis, have been reported.…”

Asp Viper (Vipera aspis) Envenomation: Experience of the Marseille Poison Centre from 1996 to 2008

“…The phospholipase A2 neurotoxins present in the venom of some asp vipers in France are similar to the neurotoxins (vipoxin and ammodytoxins) found in Vipera ammodytes (Table 1) [3,4,5,6,7,8,9,10,11,12]. Venom from Vipera ammodytes is used to immunize horses for production of Viperfav*.…”

“…Both contain kininogenase (hypotensive bradykinin-releasing enzyme), prothrombin-activating factors, proteases, and hyaluronidases. Neurotoxins of the phospholipase A2 type have been found in the venom of some populations of Vipera aspis, but never in the venom of Vipera berus (Table 1) [3,4,5,6,7,8,9,10,11,12]. …”