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Toxins and Drug Discovery pp 3–20Cite as

Crotoxin from Crotalus durissus terrificus and Crotoxin-Related Proteins: Structure and Function Relationship

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Part of the book series: Toxinology ((TOXI))

Abstract

Snake venom presynaptic phospholipases A2 (PLA2s) are β-neurotoxins present in monomeric form or as multimeric complexes with various quaternary structures. Three classes of β-neurotoxins from snake venom have been described. Here in the heterodimeric CACB crotoxin complex, a potent β-neurotoxin from Crotalus durissus terrificus venom, and its natural isoforms are presented. Crotoxin and crotoxin-related proteins possess PLA2 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 PLA2-receptor targets. Mono- and multimeric PLA2s are involved in various biological functions and can modulate specific disease processes. Numerous attempts have been made to correlate PLA2 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 PLA2-receptor complexes have been reported. The acidic CA subunit of crotoxin may be considered as a natural target of the basic PLA2 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.

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Authors and Affiliations

  1. Département de Neuroscience, Institut Pasteur, Unité Récepteurs-Canaux, CNRS, UMR 3571, Paris, France

    Grazyna Faure & Dorota Porowinska

  2. Department of Biochemistry, Nicolaus Copernicus University, Torun, Poland

    Dorota Porowinska

  3. Institut Pasteur, Plate-forme de Cristallographie, CNRS-UMR 3528, Paris, France

    Frederick Saul

Authors
  1. Grazyna Faure
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  2. Dorota Porowinska
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  3. Frederick Saul
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Correspondence to Grazyna Faure .

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Editors and Affiliations

  1. Marine Science Institute, University of the Philippines Diliman, Quezon City, Philippines

    Lourdes J. Cruz

  2. Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou Hainan University, Haikou, Hainan, China

    Sulan Luo

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Faure, G., Porowinska, D., Saul, F. (2017). Crotoxin from Crotalus durissus terrificus and Crotoxin-Related Proteins: Structure and Function Relationship. In: Cruz, L., Luo, S. (eds) Toxins and Drug Discovery. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6452-1_7

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