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Structure-Function Relationship in Heterodimeric Neurotoxin PLA2s from Viperidae Snakes Inhabiting Europe, South America, and Asia

Functional Importance of the Nontoxic Components

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Venom Genomics and Proteomics

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

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Abstract

Snake venom heterodimeric non-covalent phospholipase A2 (PLA2) complexes (ncHdPLA2s) are neurotoxins encountered in the venoms of Viperinae and Crotalinae snakes. In contrast to their monomeric counterparts, they have a sophisticated mechanism of action in order to avoid nonspecific binding to “wrong” targets and to increase the efficiency of the pharmacological attack. ncHdPLA2s consist of a toxic and enzymatically active basic PLA2 and an acidic and catalytically inactive PLA2 protein. The main function of the acidic subunit is to direct the toxic component to the “correct” targets on the cell membrane and in this way to avoid binding to phospholipids, which are not important for the pharmacological effect of the toxin. The nontoxic component of ncHdPLA2s is multifunctional. It can modulate the toxicity and catalytic activity of PLA2.

The structure and function of ncHdPLA2s from the venoms of snakes inhabiting Europe, South America, and Asia are similar. There exists a high identity at the levels of primary and three-dimensional structures of ncHdPLA2s from snakes inhabiting widely separated regions of the world. Although a substantial progress has been made during the last years in understanding the structure and biological action of ncHdPLA2s, a number of questions still remain to be answered.

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Authors and Affiliations

  1. Institute of Biochemistry and Molecular Biology, Laboratory of Structural Biology of Infection and Inflammation, University of Hamburg, c/o DESY, Notkestr. 85, Building 22a, 22603, Hamburg, Germany

    Dessislava Georgieva & Christian Betzel

  2. Department of Physics, Multi User Center for Biomolecular Innovation, Institute of Biosciences, Humanities and Physical Sciences, IBILCE/UNESP (Universidade Estadual Paulista), Cristóvão Colombo 2265, CEP 15054-000, São José do Rio Preto, SP, Brazil

    Raghuvir K. Arni

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  1. Dessislava Georgieva
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  2. Raghuvir K. Arni
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  3. Christian Betzel
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Correspondence to Christian Betzel .

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  1. Venom and Toxin Research Programme, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Structural and Functional Venomics Lab, Instituto de Biomedicina de Valencia (CSIC), Valencia, Spain

    Juan J. Calvete

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Georgieva, D., Arni, R.K., Betzel, C. (2016). Structure-Function Relationship in Heterodimeric Neurotoxin PLA2s from Viperidae Snakes Inhabiting Europe, South America, and Asia. In: Gopalakrishnakone, P., Calvete, J. (eds) Venom Genomics and Proteomics. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6416-3_16

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