X-RAY STRUCTURE OF VIPOXIN, A COMPLEX BETWEEN A TOXIC PHOSPHOLIPASE A2 AND ITS NATURAL INHIBITOR. Ch. Betzel^*, M. Perbandt^*, T. S. Singh^**, N. Genov^***, ^*Institute of Physiological Chemistry c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany, ^**Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110020, India, ^***Institute of Organic Chemistry, Bulgarian Academy of Sciences, Sofia 1040, Bulgaria

The toxin Vipoxin is the first complex found between a basic toxic phospholipase A₂ and an acidic non-toxic protein inhibitor. It is found in the venom of the Bulgarian viper (Vipera ammodytes ammodytes), the most toxic snake in Europe. The two polypeptide chains each consist of 122 residues and are highly homologous (62%). The Vipoxin complex is also the first reported and intriguing example of high structural homology between an enzyme and its natural inhibitor. Several homologous toxic phospholipases A₂ have been characterized, however except the PLA₂ of Vipoxin none of them form a complex with a natural inhibitor and all represent toxins with a presynaptic action. In contrast Vipoxin is a neurotoxin with postsynaptic action and also little is known about snake venom inhibitors so far. The three-dimensional structure of Vipoxin sheds light on the detailed relationship between the PLA₂ and its inhibitor. X-ray data were collected using synchrotron radiation; the structure was solved by molecular replacement. Details about the structure solution and refinement as well as the structure function relationship will be presented The three-dimensional structure of Vipoxin allows a detailed description of the active site of the toxic PLA₂ and the means of its inhibitor.