Journal of Environment and Sociobiology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

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


Affiliations
1 Department of Zoology, B. C. College, Asansol, West Bengal, India
2 Department of Zoology, Vivekananda College, Kolkata, West Bengal, India
     

   Subscribe/Renew Journal


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.

Keywords

Phospholipase A2, Adamsia palliata, Cytotoxicity, Amphitropic Protein, TRPV1 Channel.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Alberts, B., Bray, D., Hopkin, K., Johnson, A. D., Lewis, J., Raff, M., Roberts, K. and Walter, P. 2010. Essential Cell Biology (Third edition). Garland Science/Taylor & Francis Group: New York and London.

  • Andreev, Y. A., Kozlov, S. A., Koshelev, S. G., Ivanova, E A., Monastyrnaya, M. M., Kozlovskaya, E. P. and Grishin, E. V. 2008. Analgesic compound from sea anemone Heteractis crispa is the first polypeptide inhibitor of vanilloid receptor 1 (TRPV1). J. Biol. Chem., 283: 23914-23921.

  • Aparna, K., Priyakumari, C. J. and Kezia, J. G. 2015. Homology Modelling, secondary structure prediction and phylogenetic comparative analysis of Phospholipase A2 from different organism. International Journal of Pharmaceutical Sciencies and Research, 6(2): 636-644.

  • Argiolas, A. and Pisano, J. J. 1983. Facilitation of phospholipase A2 activity by mastoparans, a new class of mast cell degranulating peptides from wasp venom. The Journal of Biological Chemistry, 258 (22): 13697-13702.

  • Arnold, K., Bordoli, L., Kopp, J. and Schwede, T. 2006. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling. Bioinformatics, 22: 195-201.

  • Bechinger, B., Gierasch, L. M., Montal, M., Zasloff, M. and Opella, S. J. 1996. Orientations of helical peptides in membrane bilayers by solid state NMR spectroscopy. Solid State Nucl. Maqn. Reson., 7(3): 185-191.

  • Berg, O. G., Gelb, M. H., Tsai, M. D. and Jain, M. K. 2001. Interfacial enzymology: the secreted phospholipase A(2)-paradigm. Chemical Reviews, 101 (9): 2613-2654.

  • Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., Shindyalov, I. N. and Bourne, P. E. 2000. The Protein Data Bank. Nucleic Acids Research, 28: 235-242.

  • Bowie, J. U., Luthy, R. and Eisenberg, D.1991. A method to identify protein sequences that fold into a novel three dimensional structure. Science, 253 (5016): 164-170.

  • Christopher, J., Bohlen J. and David, J. 2012. Receptor-targeting mechanisms of pain-causing toxins: How ow? Toxicon, 60(3): 254-264.

  • Comeau, S. R., Gatchell, D. W., Vajda, S. and Camacho, C. J. 2004. ClusPro: an automated docking and discrimination method for the prediction of protein complexes. Bioinformatics, W96-99.

  • Cornelius, P. F. S. and Ates. R. M. L. 2003. On the name of the hermit-crab anemone, Adamsia palliata (O. F. Müller, 1776). Zoologische Verhandelingen, 345: 85-87.

  • Cuypers, E., Peigneur, S., Debaveye, S., Shiomi, K. and Tytgat, J. 2011. TRPV1 Channel as new target for marine toxins: Example of gigantoxin I, a Sea Anemone toxin acting via modulation of the PLA2 pathway. Acta Chim. Slov., 58(4):735-41.

  • Ezzeddini, R., Darabi, M., Ghasemi, B., Jabbari Moghaddam, Y., Jabbari, Y., Abdollahi, S., Rashtchizadeh, N., Gharahdaghi, A., Darabi, M., Ansarin, M., Shaaker, M., Samadi, A. and Karamravan, J. 2012. Circulating phospholipase-A2 activity in obstructive sleep apnea and recurrent tonsillitis. International Journal of Pediatric Otorhinolaryngology, 76(4): 471-474.

  • Gautier, R., Douguet, D., Anthonny, B. and Drin, G. 2008 Heliquest: aweb-server to screen sequences with specific α-helical properties. Bioinformatics, 24(18): 2101-2102.

  • Gofman, Y., Haliloglu, T. and Ben, N. 2012. Monte Carlo simulation of peptide membrane with the McPep web-server. Nucleic Acid Res., 40(W1): W358-W363.

  • Johansson, M. U., Zoete, V., Michielin, O. and Guex, N. 2012. Defining and searching for structural motifs using Deepview/ Swiss PDB-Viewer. BMC Bioinfomatics, 13: 173.

  • Kastritis, P. L. and Bonvin, A. M. 2010. Are scoring functions in protein-protein docking ready to clues from a novel binding affinity benchmark predict interactomes? J. Proteome Res., 9(5): 2216-2225.

  • Kaur, R. 2015, Homology based modeling of CryC2 toxin and SIAPN receptor and in silico docking of the derived structures. Modeling and Docking of Toxin and Receptor Molecules, pp: 111-125.

  • Keller, R. C. 2014. Identification and in silico analysis of helical lipid binding regions in proteins belonging to the amphitropic protein family. J. Biosci., 39(5): 771-783.

  • Kimmett, T., Smith, N., Witham, S., Petukh, M., Sarkar, S. and Alexov, E. 2014. ProBLM web server: protein and membrane placement and orientation package. Comput. Math. Methods Med., 2014: 838259.

  • Kym, P. R., Kort, M. E. and Hutchins, C. W. 2009. Analgesic potential of TRPV1 antagonists. Biochemical Pharmacology, 78(3): 211-216.

  • Laskowski, R. A., MacArthur, M. W., Moss, D. S. and Thornton, J. M. 1993. PROCHECK- a program to check the stereochemical quality of protein structures. J. App. Cryst., 26: 283-291.

  • Laskowski, R. A., Luscombe, N. M., Swindells, M. B. and Thornton, J. M. 1996. Protein clefts in molecular recognition and function. Protein Sci., 5(12): 2438-2452.

  • Lau, S. Y., Procko, E. and Gaudet, R. 2012. Distinct properties of Ca2+-calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel. J. Gen. Physiol., 140: 541-555.

  • Lengauer, T. and Rarey, M. 1996. Computational methods for biomolecular docking. Current Opinion in Structural Biology, 6(3): 402-406.

  • Mallat, Z., Lambeau. G. and Tedgui, A. 2010. Lipoprotein-associated and secreted phospholipases A2 in cardiovascular disease: roles as biological effectors and biomarkers. Circulation, 122 (21): 2183-2200.

  • McCulloch, J., Uddman, R., Kingman, T. A. and Edvinsson, L. 1996. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc. Natl. Acad. Sci., U S A., 83(15): 5731-5735.

  • Melo, F., Devos, D., Depiereux, E. and Feytmans, E. 1997. ANOLEA: a www server to assess protein structures. Intelligent Systems for Molecular Biology, 97: 110-113.

  • Mount, D. M. 2004. Bioinformatics: Sequence and Genome Analysis (2 ed.). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN 0-87969-712-1.

  • Rawlings, C. J., Taylor, W,.R., Nyakairu, J., Fox, J. and Sternberg, M. J. E. 1985. Reasoning about protein topology using the logic programming language PROLOG. Journal of Molecular graphics, 3(4): 151-157.

  • Ricciotti, E. and FitzGerald Garret, A. 2011. Prostaglandins and inflammations. Arterioscler Thromb Vasc. Biol., 31(5): 986-1000.

  • Romero, L., Marcussi, S., Marchi-Salvador, D. P., Silva, F. P., Jr Fuly, A. L., Stabeli, R. G., da Silva, S. L., Gonzalez, J., Monte, A. D. and Soares, A. M. 2010. Enzymatic and structural characterization of a basic phospholipase A(2) from the sea anemone Condylactis gigantea. Biochimie, 92: 1063-1071.

  • Shim, W. S., Tak, M. H., Lee, M. H. Kim, M., Kim, M., Koo, J. Y., Lee, C. H., Kim, M. and Oh, U. 2007. TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12- lipoxygenase. J. Neurosci., 27(9): 2331-2337.

  • Smith, N., Campbell, B. Chuan Li, L. L. and Alexov, E. 2012. Protein Nano-Object Integrator (ProNOI) for generating atomic style objects for molecular modeling BMC Struct. Biol., 5: 12.

  • Suh, Y. G. and Oh, U. 2005. Activation and activators of TRPV1 and their pharmaceutical implication. Current Pharmaceutical Design, 11(21): 2687-2698.

  • Taylor, K., Nicholas, S., Shawn, W., Marharyta, P., Sarkar, S. and Emil, A. 2014. ProBLM Web Server: Protein and membrane placement and orientation package. Computational and Mathematical Methods in Medicine, Vol. 2014, Article ID 838259, 7 pages.

  • Uniprot Consortium. 2014. UniProt: a hub for protein information. Nucleic Acids Research, 43(D1): D204-D212.

  • Wallace, A. C., Laskowski, R. A. and Thornton, J. M. 1995. LIGPLOT+: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 8(2): 127-134.

  • Wiederstein, M. and Sippl, M. J. 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 35(2): W407-410.

  • Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J. and Zhang, Y. 2015. The I-TASSER Suite: Protein structure and function prediction. Nature Methods, 12: 7-8.

  • Zaharenko, A. J., Schiavon, E., Ferreira, W. A., Lecchi, J., Freitas, J. C., Richardson, M. and Wanke , E. 2012. Chracterization of selectively and pharmacophores of type 1 sea anemone toxins by screening seven Na sodium channel isoforms. Peptides, 34 (1): 158-167.


Abstract Views: 472

PDF Views: 1




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

Abstract Views: 472  |  PDF Views: 1

Authors

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

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.

Keywords


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

References