title: Crystal structure of vipoxin at 2.0 A: an example of regulation of a toxic function generated by molecular evolution.
abstract: 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 A2 (PLA2) 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 PLA2 activity is of great pharmacological interest, and the present structure will be a model for structure-based drug design.
authors.affiliation: Institute of Biochemistry, Free University of Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Perbandt
authors.forename: J C
authors.initials: JC
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Eschenburg
authors.forename: I
authors.initials: I
authors.lastname: Mancheva
authors.forename: B
authors.initials: B
authors.lastname: Aleksiev
authors.forename: N
authors.initials: N
authors.lastname: Genov
authors.forename: P
authors.initials: P
authors.lastname: Willingmann
authors.forename: W
authors.initials: W
authors.lastname: Weber
authors.forename: T P
authors.initials: TP
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Betzel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D054467:Phospholipases A2; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D014757:Viper Venoms / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D009498:Neurotoxins; D010726:Phosphodiesterase Inhibitors; D014757:Viper Venoms; C033134:vipoxin; D010741:Phospholipases A; D054467:Phospholipases A2