Endogenous phospholipase A2 inhibitors in snakes: a brief overview.

Patrícia Cota Campos,Gabriel Latorre Fortes Dias,Lutiana Amaral De Melo,Consuelo Latorre Fortes-Dias

doi:10.1186/s40409-016-0092-5

Patrícia Cota Campos, Gabriel Latorre Fortes Dias + Show 2 more

Open Access

https://doi.org/10.1186/s40409-016-0092-5

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Abstract

The blood plasma of numerous snake species naturally comprises endogenous phospholipase A2 inhibitors, which primarily neutralize toxic phospholipases A2 that may eventually reach their circulation. This inhibitor type is generally known as snake blood phospholipase A2 inhibitors (sbPLIs). Most, if not all sbPLIs are oligomeric glycosylated proteins, although the carbohydrate moiety may not be essential for PLA2 inhibition in every case. The presently known sbPLIs belong to one of three structural classes – namely sbαPLI, sbβPLI or sbγPLI – depending on the presence of characteristic C-type lectin-like domains, leucine-rich repeats or three-finger motifs, respectively. Currently, the most numerous inhibitors described in the literature are sbαPLIs and sbγPLIs, whereas sbβPLIs are rare. When the target PLA2 is a Lys49 homolog or an Asp49 myotoxin, the sbPLI is denominated a myotoxin inhibitor protein (MIP). In this brief overview, the most relevant data on sbPLIs will be presented. Representative examples of sbαPLIs and sbγPLIs from two Old World – Gloydius brevicaudus and Malayopython reticulatus – and two New World – Bothrops alternatus and Crotalus durissus terrificus – snake species will be emphasized.

Highlights

A number of venomous and nonvenomous snake species are naturally resistant to the deleterious actions of snake venom components, in many cases due to the presence of specific antitoxins in their circulating blood [1,2,3,4,5,6,7,8,9,10]
The first authors to identify various Snake blood phospholipase inhibitor (sbPLI) in a single snake species – Gloydius brevicaudus, formerly Agkistrodon blomhoffii siniticus – proposed a classification based on the presence of characteristic domains of known mammalian proteins in their structure and on variations in their Phospholipase A2 (PLA2) selectivity [12]
Chimeric constructions of GbαPLI and the non-functional sbαPLI homolog from E. quadrivirgata allowed the mapping of important amino acids for PLA2 inhibition in the 13–36 segment, which are expected to be located in the helical neck of the GbαPLI trimer based on the threedimensional structural model constructed by homology modeling [29, 30]

Summary

Introduction

A number of venomous and nonvenomous snake species are naturally resistant to the deleterious actions of snake venom components, in many cases due to the presence of specific antitoxins in their circulating blood [1,2,3,4,5,6,7,8,9,10]. The first authors to identify various sbPLIs in a single snake species – Gloydius brevicaudus, formerly Agkistrodon blomhoffii siniticus – proposed a classification based on the presence of characteristic domains of known mammalian proteins in their structure and on variations in their PLA2 selectivity [12]. Gamma inhibitors (sbγPLIs) display a threefinger pattern and are less specific than the aforementioned classes, inhibiting neutral, acidic and basic PLA2s from snake venoms.

Results

Conclusion