Comparative Structural Analysis of Phospholipase A2 and Combinatorial Screening of PLA2 Inhibitors

International Journal of Biometric and Bioinformatics

Jignesh Savani¹  Joy Harris Hoskeri¹  Mayank Agrawal¹  Sarnim Gurung¹  Vedamurthy A.B.¹  Roshan Adhikari¹  Sanjay Sharma Timilsina¹ 

关键词: Phospholipase A2;    Antivenom Drugs;    Superimposition Studies;    Sequence Alignment;    Combinatorial Screening;    Molecular Docking.;   

DOI  :  

学科分类：计算机科学（综合）

来源: Computer Science Journals

【 摘 要 】

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 andcatalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids. PLA2 arecommonly found in mammalian tissues as well as in insects and snakes venom. Venomsconstitute a rich source of phospholipase A2 (PLA2) enzymes, which show remarkable diversityin their structure and function. In this investigation, we have made an attempt in analyzing theidentical active domain in different PLA2 protein structure isolated from different venoms bystudying the conserved active pocket residues. The 21 crystal structures of different PLA2enzymes isolated from venoms of different species were studied and collected from PDBdatabase. Comparative studies to analyse the conserved active site in this protein was carried outby superimposition studies using TOPMATCH server. To validate the superimposition resultssequence alignment studies was carried out using T-COFFEE by multiple sequence alignmentanalysis. This revealed that 9 PLA2 enzymes from different venoms viz., Daboia russellii,Cerrophidion godmani, Dienagkistrodon acutus, Bothrops Neuwied, Agkistrodon contortrix, Najasagittifera, Bos Taurus, Notechis sentatusscutatus, Apis mellifera showed similarity in their activepocket residues, indicating a single drug can effectively occupy their pocket and inhibit thefunctions of these nine proteins. Hence, in-silico drug designing studies for antivenom drugsagainst PLA2 was carried out by combinatorial screening of 18 antivenom compounds by dockingwith PLA2 molecule using Autodock 3.0 tool. In-silico drug designing studies revealed that among18 antivenom compounds, Indole was most potent in its action in inhibiting the PLA2 function withinhibition constant of 0.04.

【 授权许可】

Unknown