Ensemble-based molecular docking and spectrofluorometric analysis of interaction between cytotoxin and tumor necrosis factor receptor 1.

Autor:	Misuan N; School of Science, Monash University Malaysia, Bandar Sunway, Malaysia., Mohamad S; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), University of Malaya, Kuala Lumpur, Malaysia., Tubiana T; CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, Gif-sur-Yvette, France., Yap MKK; School of Science, Monash University Malaysia, Bandar Sunway, Malaysia.; Tropical Medicine and Biology Multidisciplinary Platform, Bandar Sunway, Malaysia.
Jazyk:	angličtina
Zdroj:	Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023; Vol. 41 (24), pp. 15339-15353. Date of Electronic Publication: 2023 Mar 16.
DOI:	10.1080/07391102.2023.2188945
Abstrakt:	Cytotoxin (CTX) is a three-finger toxin presents predominantly in cobra venom. The functional site of the toxin is located at its three hydrophobic loop tips. Its actual mechanism of cytotoxicity remains inconclusive as few conflicting hypotheses have been proposed in addition to direct cytolytic effects. The present work investigated the interaction between CTX and death receptor families via ensemble-based molecular docking and fluorescence titration analysis. Multiple sequence alignments of different CTX isoforms obtained a conserved CTX sequence. The three-dimensional structure of the conserved CTX was later determined using homology modelling, and its quality was validated. Ensemble-based molecular docking of CTX was performed with different death receptors, such as Fas-ligand and tumor necrosis factor receptor families. Our results showed that tumor necrosis factor receptor 1 (TNFR1) was the best receptor interacting with CTX attributed to the interaction of all three functional loops and evinced with low HADDOCK, Z -score and RMSD value. The interaction between CTX and TNFR1 was also supported by a concentration-dependent reduction of fluorescence intensity with increasing binding affinity. The possible intermolecular interactions between CTX and TNFR1 were Van der Waals forces and hydrogen bonding. Our findings suggest a possibility that CTX triggers apoptosis cell death through non-covalent interactions with TNFR1.Communicated by Ramaswamy H. Sarma.
Databáze:	MEDLINE
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