title: Vipoxin and its components: structure-function relationship.
abstract: The neurotoxin Vipoxin has been of growing research interest since the time of its isolation from the venom of the Bulgarian viper Vipera ammodytes meridionalis. Vipoxin is a heterodimeric postsynaptic ionic complex composed of two protein subunits-a basic and strongly toxic His48 secretory phospholipase A(2) (sPLA(2)) enzyme and an acidic, enzymatically inactive and nontoxic component, originally named Inhibitor. When separated, sPLA(2) enzyme loses its toxicity in 3-4 days and catalytic activity in 2 weeks. After the establishment of the high degree of sequence homology (62%) and crystal structure of the subunits, Vipoxin was served as an example of molecular evolution of a toxic but unstable sPLA(2) into an inhibitor subunit which stabilizes the enzyme and preserves its pharmacological activity. Beginning our research on Vipoxin, intrigued by the unique relationship-structure-function and based on the previous experience, we were more than surprised to establish the lack of so-called inhibitory function of the acidic subunit on the toxicity and catalytic activity of basic sPLA(2). On the contrary, the acidic subunit activated the sPLA(2) enzyme in vitro. Our studies undoubtedly proved that is more correctly to present Vipoxin as a heterodimeric complex composed of one basic catalytic subunit and one acidic regulatory subunit. Their interaction in a common quaternary protein structure is more than a noncovalent association between the two subunits. It allows pharmacological sites to be targeted and biological functions to be potentiated. We attempt to present the previous studies and new findings on Vipoxin and its components.
authors.affiliation: Laboratory of Enzymology, Department of Biochemistry, Faculty of Biology, Sofia University, Sofia, Bulgaria.
authors.forename: S D
authors.initials: SD
authors.lastname: Petrova
authors.forename: V N
authors.initials: VN
authors.lastname: Atanasov
authors.forename: K
authors.initials: K
authors.lastname: Balashev
mesh_terms: D055162:Biocatalysis; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*
chemical_list: D014757:Viper Venoms; C033134:vipoxin; D054467:Phospholipases A2