Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom

Presynaptic neurotoxins are one of the major components in Bungarus venom. Unlike other Bungarus species that have been studied, β-bungarotoxin has never been isolated from Bungarus fasciatus venom. It was hypothesized that the absence of β-bungarotoxin in this species was due to divergence during e...

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Main Authors:	Ahmad Rusmili, Muhamad Rusdi, Ting, Tee Yee, Mustafa, Mohd Rais, Hodgson, Wayne C., Othman, Iekhsan
Format:	Article
Language:	English English English
Published:	Elsevier Inc. 2014
Subjects:	QH301 Biology RM300 Drugs and their action
Online Access:	http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/1/2014_Rusmili_BiochemPharma_Presynaptic.pdf http://irep.iium.edu.my/37576/4/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_SCOPUS.pdf http://irep.iium.edu.my/37576/5/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_WoS.pdf

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spelling	iium-375762017-09-06T00:36:47Z http://irep.iium.edu.my/37576/ Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom Ahmad Rusmili, Muhamad Rusdi Ting, Tee Yee Mustafa, Mohd Rais Hodgson, Wayne C. Othman, Iekhsan QH301 Biology RM300 Drugs and their action Presynaptic neurotoxins are one of the major components in Bungarus venom. Unlike other Bungarus species that have been studied, β-bungarotoxin has never been isolated from Bungarus fasciatus venom. It was hypothesized that the absence of β-bungarotoxin in this species was due to divergence during evolution prior to evolution of β-bungarotoxin. In this study, we have isolated a β-bungarotoxin isoform we named P-elapitoxin-Bf1a by using gel filtration, cation-exchange and reverse-phase chromatography from Malaysian B. fasciatus venom. The toxin consists of two heterogeneous subunits, subunit A and subunit B. LCMS/MS data showed that subunit A was homologous to acidic phospholipase A2 subunit A3 from B. candidus and B. multicinctus venoms, whereas subunit B was homologous with subunit B1 from Bungarus fasciatus venom that was previously detected by cDNA cloning. The toxin showed concentration- and time-dependent reduction of indirect-twitches without affecting contractile responses to ACh, CCh or KCl at the end of experiment in the chick biventer preparation. Toxin modification with 4-BPB inhibited the neurotoxic effect suggesting the importance of His-48. Tissue pre-incubation with monovalent B. fasciatus (BFAV) or neuro polyvalent antivenom (NPV), at the recommended titer, was unable to inhibit the twitch reduction induced by the toxin. This study indicates that Malaysian B. fasciatus venom has a unique β-bungarotoxin isoform which was not neutralised by antivenoms. This suggests that there might be other presynaptic neurotoxins present in the venom and there is a variation in the enzymatic neurotoxin composition in venoms from different localities. Elsevier Inc. 2014 Article PeerReviewed application/pdf en http://irep.iium.edu.my/37576/1/2014_Rusmili_BiochemPharma_Presynaptic.pdf application/pdf en http://irep.iium.edu.my/37576/4/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_SCOPUS.pdf application/pdf en http://irep.iium.edu.my/37576/5/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_WoS.pdf Ahmad Rusmili, Muhamad Rusdi and Ting, Tee Yee and Mustafa, Mohd Rais and Hodgson, Wayne C. and Othman, Iekhsan (2014) Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom. Biochemical Pharmacology, 91 (3). pp. 409-416. ISSN 0006-2952 http://www.sciencedirect.com/science/article/pii/S0006295214003888 http://dx.doi.org/10.1016/j.bcp.2014.07.001
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	QH301 Biology RM300 Drugs and their action
spellingShingle	QH301 Biology RM300 Drugs and their action Ahmad Rusmili, Muhamad Rusdi Ting, Tee Yee Mustafa, Mohd Rais Hodgson, Wayne C. Othman, Iekhsan Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
description	Presynaptic neurotoxins are one of the major components in Bungarus venom. Unlike other Bungarus species that have been studied, β-bungarotoxin has never been isolated from Bungarus fasciatus venom. It was hypothesized that the absence of β-bungarotoxin in this species was due to divergence during evolution prior to evolution of β-bungarotoxin. In this study, we have isolated a β-bungarotoxin isoform we named P-elapitoxin-Bf1a by using gel filtration, cation-exchange and reverse-phase chromatography from Malaysian B. fasciatus venom. The toxin consists of two heterogeneous subunits, subunit A and subunit B. LCMS/MS data showed that subunit A was homologous to acidic phospholipase A2 subunit A3 from B. candidus and B. multicinctus venoms, whereas subunit B was homologous with subunit B1 from Bungarus fasciatus venom that was previously detected by cDNA cloning. The toxin showed concentration- and time-dependent reduction of indirect-twitches without affecting contractile responses to ACh, CCh or KCl at the end of experiment in the chick biventer preparation. Toxin modification with 4-BPB inhibited the neurotoxic effect suggesting the importance of His-48. Tissue pre-incubation with monovalent B. fasciatus (BFAV) or neuro polyvalent antivenom (NPV), at the recommended titer, was unable to inhibit the twitch reduction induced by the toxin. This study indicates that Malaysian B. fasciatus venom has a unique β-bungarotoxin isoform which was not neutralised by antivenoms. This suggests that there might be other presynaptic neurotoxins present in the venom and there is a variation in the enzymatic neurotoxin composition in venoms from different localities.
format	Article
author	Ahmad Rusmili, Muhamad Rusdi Ting, Tee Yee Mustafa, Mohd Rais Hodgson, Wayne C. Othman, Iekhsan
author_facet	Ahmad Rusmili, Muhamad Rusdi Ting, Tee Yee Mustafa, Mohd Rais Hodgson, Wayne C. Othman, Iekhsan
author_sort	Ahmad Rusmili, Muhamad Rusdi
title	Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
title_short	Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
title_full	Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
title_fullStr	Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
title_full_unstemmed	Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom
title_sort	isolation and characterization of a presynaptic neurotoxin, p-elapitoxin-bf1a from malaysian bungarus fasciatus venom
publisher	Elsevier Inc.
publishDate	2014
url	http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/ http://irep.iium.edu.my/37576/1/2014_Rusmili_BiochemPharma_Presynaptic.pdf http://irep.iium.edu.my/37576/4/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_SCOPUS.pdf http://irep.iium.edu.my/37576/5/37576_Isolation%20and%20characterization%20of%20a%20presynaptic%20neurotoxin_WoS.pdf
first_indexed	2023-09-18T20:53:55Z
last_indexed	2023-09-18T20:53:55Z
_version_	1777410176893059072

Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian bungarus fasciatus venom

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