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

• Published in: FEBS letters Vol. 412; no. 3; pp. 573 - 577
• Main Authors: Perbandt, M, Wilson, J.C, Eschenburg, S, Mancheva, I, Aleksiev, B, Genov, N, Willingmann, P, Weber, W, Singh, T.P, Betzel, Ch
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 04.08.1997
• Subjects: Amino Acid Sequence; Animals; Crystallography, X-Ray; Dimerization; Evolution, Molecular; Molecular Sequence Data; Neurotoxins - antagonists & inhibitors; Neurotoxins - chemistry; Neurotoxins - toxicity; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Phospholipases A - antagonists & inhibitors; Phospholipases A - chemistry; Phospholipases A - toxicity; Phospholipases A2; PLA 2-complex; PLA2-complex; Protein Folding; Sequence Homology, Amino Acid; Synchrotron radiation; Viper Venoms - antagonists & inhibitors; Viper Venoms - chemistry; Viper Venoms - toxicity; Vipoxin; X-ray structure; Vipoxin; PLA 2-complex; X-ray structure; Synchrotron radiation
• DOI: 10.1016/S0014-5793(97)00853-3
• ISSN: 0014-5793

Vipoxin is the main toxic component in the venom of the Bulgarian snake Vipera ammodytes meridionalis, the most toxic snake in Europe. Vipoxin is a complex between a toxic phospholipase A 2 (PLA 2) and a non-toxic protein inhibitor. The structure is of genetic interest due to the high degree of sequence homology (62%) between the two functionally different components. The structure shows that the formation of the complex in vipoxin is significantly different to that seen in many known structures of phospholipases and contradicts the assumptions made in earlier studies. The modulation of PLA 2 activity is of great pharmacological interest, and the present structure will be a model for structure-based drug design.