HOMOLOGY MODELING OF SHORT CHAIN NEUROTOXINS: AN INITIATION TOWARDS UNDERSTANDING THEIR FUNCTIONAL INFERENCE
Keywords:
Short chain neurotoxins, Neurotoxins, Ion channels, Homology modeling, RMSD, Structural superimpositionAbstract
Objectives: Various types of venoms are being produced by different toxic species which make mild or severe damage to the biological system of target species. The main objective is to disseminate structural information in order to understand the functional importance of the short chain neurotoxins (SCNs).
Methods: Computational homology modeling technique is used to predict the theoretical 3D structure of protein. Structural qualities of all predicted SCNs are analyzed using bioinformatics tools.
Results: Homology modeling was performed for all selected SCNs (62 toxin proteins) which do not have experimental models in structural databases. Structural folding patterns of all constructed models were further analyzed for exploring the functional role of SCNs. Three dimensional structures of SCNs provide a better understanding of molecular mechanisms that underlies the inhibition of neurotransmitter based potassium ion channels.
Conclusion: The retrieved structural information of SCNs will serve as a starting point for designing suitable antidote. Future research is required for analyzing the feasibility of using venomous toxins as a pharmacological agent for several disease targets.
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References
Tsetlin V, Utkin Y, Kasheverov I. Nicotinic Receptor-Based Therapeutics:Emerging Frontiers in Basic Research & Clinical Science. J Biochem Pharmacol 2009;78:720-31.
Rees B, Bilwes A. Three-dimensional structures of neurotoxins and cardiotoxins. J Chem Res Toxicol 1993;6:385-406.
Liu Z, Li W, Zhang H, Han Y, Lai L. Modeling the third loop of short-chain snake venom neurotoxins:roles of the short-range and long-range interactions. J Proteins 2001;42:6-16.
Gong N, Armugam A, Jeyaseelan K. Postsynaptic short-chain neurotoxins from Pseudonaja textilis. cDNA cloning, expression and protein characterization. Euro J Biochem 1999;265:982-9.
Jose CN, Eliane CA, Oliveira B, Jose RG, Sergio M. TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus venom which acts on Ca2+ activated K+ channels. J Toxicon 1999;37:651-60.
Mordvintsev DY, Polyak YL, Levtsova OV, Tourleigh YV, Kasheverov IE, Shaitan KV, et al. A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from Torpedo californica:comparison with long-chain alpha-neurotoxins and alpha-conotoxins. J Comp Biol Chem 2005;29:398-411.
Tsetlin V, Utkin Y, Kasheverov I. Polypeptide and peptide toxins, magnifying lenses for binding sites in nicotinic acetylcholine receptors. J Biochem Pharmacol 2009;78:720-31.
Reid PF. Alpha-cobratoxin as a possible therapy for multiple sclerosis:a review of the literature leading to its development for this application. J Crit Rev Immunol 2007;27:291-302.
Tyler HR. Double-blind study of modified neurotoxin in motor neuron disease. J Neurol 1979;29:77-81.
Alama A, Bruzzo C, Cavalieri Z, Forlani A, Utkin Y, Casciano I, Romani M. Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins:is there a perspective in lung cancer treatment? J PLoS One 2011;6(6):e20695.
Kumar RB, Suresh MX. Computational analysis of bioactive phytochemicals as potential inhibitors for calcium activated potassium channel blocker, tamulotoxin from Mesobuthus tamulus. J Pharmacog 2013;5:41-5.
Bairoch A, Apweiler R, Wu CH, Winona CB, Boeckmann B, Ferro S, et al. The Universal Protein Resource (UniProt). J Nucleic Acids Res 2008;33:D154-9.
Sali A, Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 1993;234:779-815.
Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK:a program to check the stereochemical quality of protein structures. J Appl Crystal 1993;26:283-91.
Ramachandran G, Sasisekharan V. Conformation of polypeptides and proteins. J Adv Prot Chem 1968;38:45082.
Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A. Comparative protein structure modeling of genes and genomes. J Ann Rev Biophy Biomol Str 2000;29:291-325.
Bryant SH, Altschul SF. Statistics of sequence-structure threading. J Curr Opin Strl Biol 1995;5:236-44.
Sanchez R, Pieper U, Melo F, Eswar N, Marti-Renom MA, Madhusudhan MS, et al. Protein structure modeling for structural genomics. J Nat Strl Mol Biol 2000;7:986-90.
Kihara D, Chen H, Yang YD. Quality assessment of protein structure models. J Curr Prot Pep Sci 2009;10:216-28.
Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM:A program for macromolecular energy, minimization, and dynamics calculations. J Comp Chem 1983;4:187-217.