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Phospholipase A2, Antivenom Drugs, Superimposition Studies, Sequence Alignment, Combinatorial Screening, Molecular Docking.

Phospholipases A2 (PLA2) enzyme release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the Sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids. PLA2 are commonly found in mammalian tissues as well as in insects and snakes venom. Venoms constitute a rich source of phospholipase A2 (PLA2) enzymes, which show remarkable diversity in their structure and function. In this investigation, we have made an attempt in analyzing the identical active domain in different PLA2 protein structure isolated from different venoms by studying the conserved active pocket residues. The 21 crystal structures of different PLA2 enzymes isolated from venoms of different species were studied and collected from PDB database. Comparative studies to analyse the conserved active site in this protein was carried out by superimposition studies using TOPMATCH server. To validate the superimposition results sequence alignment studies was carried out using T-COFFEE by multiple sequence alignment analysis. This revealed that 9 PLA2 enzymes from different venoms viz., Daboia russellii, Cerrophidion godmani, Dienagkistrodon acutus, Bothrops Neuwied, Agkistrodon contortrix, Naja sagittifera, Bos Taurus, Notechis sentatusscutatus, Apis mellifera showed similarity in their active pocket residues, indicating a single drug can effectively occupy their pocket and inhibit the functions of these nine proteins. Hence, in-silico drug designing studies for antivenom drugs against PLA2 was carried out by combinatorial screening of 18 antivenom compounds by docking with PLA2 molecule using Autodock 3.0 tool. In-silico drug designing studies revealed that among 18 antivenom compounds, Indole was most potent in its action in inhibiting the PLA2 function with inhibition constant of 0.04.