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7237793 
Journal Article 
Crotoxin from Crotalus durissus terrificus and Crotoxin-Related Proteins: Structure and Function Relationship 
Faure, G; Porowinska, D; Saul, F; , 
2017 
SPRINGER 
DORDRECHT 
TOXINS AND DRUG DISCOVERY 
3-20 
WOS:000415219600002 
Snake venom presynaptic phospholipases A(2) (PLA(2)s) are beta-neurotoxins present in monomeric form or as multimeric complexes with various quaternary structures. Three classes of beta-neurotoxins from snake venom have been described. Here in the heterodimeric CACB crotoxin complex, a potent beta-neurotoxin from Crotalus durissus terrificus venom, and its natural isoforms are presented. Crotoxin and crotoxin-related proteins possess PLA(2) activity and display diverse pharmacological properties. Many of these properties are conferred by regions of the structure not involved in catalysis but directly implicated in protein-protein interactions (PPI) with PLA(2)-receptor targets. Mono-and multimeric PLA(2)s are involved in various biological functions and can modulate specific disease processes. Numerous attempts have been made to correlate PLA(2) structures with these pharmacological properties and to identify PPI sites. These sites represent potential lead structures for the development of new compounds for modulation of specific disease processes. However, PPI sites are difficult to discover and design in the absence of 3D structural studies (co-crystallization with protein targets), and few structures of PLA(2)-receptor complexes have been reported. The acidic CA subunit of crotoxin may be considered as a natural target of the basic PLA(2) CB subunit. The 3D structure of the crotoxin CACB complex provides a detailed structural model of the interaction between the CA and CB subunits. Identification of the molecular interface between the two subunits of crotoxin is essential to predict other biologically relevant PPI sites. This chapter is focussed on the structure-function relationship of crotoxin and crotoxin-related proteins and recent investigations to identify new biological targets of crotoxin. 
Cruz, LJ; Luo, S; Gopalakrishnakone, P; 
978-94-007-6451-4