Studies on Mode of Action of Cnidarian PLA2 Toxin from Adamsia palliata in Triggering Cytotoxicity in Human: an in Silico Approach

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Authors

  • Sriparna Ray
     Department of Zoology, B. C. College, Asansol, West Bengal ,IN
  • Jayanta Sinha
     Department of Zoology, Vivekananda College, Kolkata, West Bengal ,IN

Keywords:

Phospholipase A2, Adamsia palliata, Cytotoxicity, Amphitropic Protein, TRPV1 Channel.

Abstract

Adamsia palliata releases Phospholipase A2 (PLA2) toxins of secretory nature. Phospholipase A2 toxin is predicted to act in two different ways. It either acts on TRPV1 channel in human by blocking them or may disrupt cell membrane and seem to catalyze the hydrolysis of 2-acyl ester bonds of 3-sn-phospholipids producing arachidonic acid and lysophospholipids through protein lipid interaction. This study attempts to in silico portray the bimodal action of PLA2 toxin by docking with Human TRPV1 receptor (Transient receptor potential vanilloid receptor1) and through PLA2 - lipid membrane interaction. Homology modeling of the PLA2 enzyme is performed through Swissmodel. Validation of 3D structure of modeled PLA2 toxin was carried out through servers, such as, ANOLEA, Prosa-II and Verify 3D. Cleft analysis and protein topology of both PLA2 toxin and TRPV1 receptor are carried out by PDBsum. Binding sites of both receptor and ligand were predicted through I-Tasser server. Docking of PLA2 toxin with TRPV1 receptor was analyzed through Cluspro docking server. Ramachandran plot of the docked model was determined through Prochek server. Seqmol server was used to predict the Kd value of the docked protein. Protein-protein interaction and determining H-bonded and non-bonded contacts between amino acids of PLA2 and TRPV1 receptor is performed through Ligplot program. Heliquest sotware was used to characterize lipid binding helices of PLA2 toxin and its physiochemical properties, such as, hydrophobicity, hydrophobic moment and net charge. Monte Carlo simulation of peptide (PLA2) and membrane lipid interaction were carried out through McPep server and diagrammatized using VLC media player. PLA2 toxin and cell membrane interaction and orientation in silico were visualized through ProBLM server. In silico study of this PLA2 toxin predicted that PLA2 may act through two different pathways. One is through interacting with Human TRPV1 receptor and the other by manipulating the helical lipid binding regions of this PLA2 toxin with respect to membrane. Thus this study tried to establish the mode of action of PLA2 toxin of Adamsia palliata on human cell membrane and its subsequent cytotoxicity, thus provides an insight on mechanistic functioning and better understanding of this type of toxin.

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2016-06-01

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Volume 13, Issue 1, June 2016

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