CRYSTAL-STRUCTURE OF VIPOXIN AT 2.0-ANGSTROM - AN EXAMPLE OF REGULATION OF A TOXIC FUNCTION GENERATED BY MOLECULAR EVOLUTION

Vipoxin is the main toxic component in the venom of the Bulgarian snak e Vipera ammodytes meridionalis, the most toxic snake in Europe, Vipox in 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 t he high degree of sequence homology (62%) between the two functionally different components, The structure shoes that the formation of the c omplex in vipoxin is significantly different to that seen in many know n structures of phospholipases and contradicts the assumptions made in earlier studies, The modulation of PLA(2) activity is of great pharma cological interest, and the present structure will be a model for stru cture-based drug design. (C) 1997 Federation of European Biochemical S ocieties.