Study on the binding interaction of three-finger toxins from cobras and mangrove catsnake toward nicotinic acetylcholine receptors: a computational approach

Zulkifli, Nor Asyikin and Ahmad Rusmili, Muhamad Rusdi and Othman, Iekhsan and Ismail, Ahmad Khaldun and Chaisakul, Janeyuth and Ibrahim, Zalikha (2022) Study on the binding interaction of three-finger toxins from cobras and mangrove catsnake toward nicotinic acetylcholine receptors: a computational approach. Journal of Pharmacy, 2 (2). pp. 122-140. E-ISSN 2773-5664

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Abstract

Introduction: Snake venom is a combination of various proteins and peptides that cause diverse biological effects in multiple organ systems. Toxins from three-finger toxin family are the mains toxins in elapid venom. Although these toxins share similarities in their structure, they are known to cause a myriad of toxic actions such as neurotoxicity, cardiotoxicity, and cytotoxicity. Unfortunately, many of these toxins are not fully pharmacologically characterized, especially on their binding affinity and selectivity towards receptors and their effects to different organ systems. Method: This work compared the binding properties of selected three-finger toxins (3FTxs) from cobras (Naja sumatrana and Naja kaouthia) and mangrove catsnake (Boiga dendrophila) towards human and bird nicotinic acetylcholine receptors (α3β2, α4β2, α7) using computational approaches. The sequence of the selected toxins were obtained from public database e.g UniProt and NCBI. The structure of the toxins without deposited structure were modelled using homology modelling. Results: The results show that all toxins bind to the orthosteric site, which is located outside the extracellular domain of α subunit for all receptors in both species. Interaction between receptors and toxins occurs by the formation of hydrogen bond, ionic bond, and hydrophobic contact with important residues involved in their binding pocket. Conclusion: Based on the data, the toxins showed different binding affinities towards nicotinic acetylcholine receptors in different species. The differences could have a significant impact on the functional characterization of venom caused by these toxins and toxins with nearly similar sequences.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Naja sumatrana, Naja kaouthia, Boiga dendrophila, binding affinity, nicotinic acetylcholine receptor, molecular docking
Subjects:	R Medicine > RM Therapeutics. Pharmacology > RM300 Drugs and their action
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy > Department of Basic Medical Sciences Kulliyyah of Pharmacy
Depositing User:	Dr Muhamad Rusdi Ahmad Rusmili
Date Deposited:	15 Aug 2022 12:29
Last Modified:	15 Aug 2022 12:31
URI:	http://irep.iium.edu.my/id/eprint/99407

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