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dc.contributor.authorBertrand, Danielen_US
dc.contributor.authorChong, Ming Zhien_US
dc.contributor.authorD'hoedt, Ddieteren_US
dc.contributor.authorFoo, Chun Shinen_US
dc.contributor.authorManjunatha Kini, R.en_US
dc.contributor.authorNirthanan, Niruen_US
dc.contributor.authorRajagopalan, Nandhaklshoreen_US
dc.contributor.authorRoy, Amritaen_US
dc.contributor.authorSivaraman, J.en_US
dc.contributor.authorZhou, Xingdingen_US
dc.date.accessioned2017-04-04T21:45:53Z
dc.date.available2017-04-04T21:45:53Z
dc.date.issued2010en_US
dc.date.modified2010-10-07T04:07:18Z
dc.identifier.issn00219258en_US
dc.identifier.doi10.1074/jbc.M109.074161en_AU
dc.identifier.urihttp://hdl.handle.net/10072/34020
dc.description.abstractSnake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (a߿d) and neuronal (a7, a3߲, and a4߲) nicotinic acetylcholine receptors (nAChRs) with highest affinity for a7-nAChRs. The high resolution (1.5 ũ crystal structure revealed haditoxin to be a homodimer, like ?-neurotoxins, which target neuronal a3߲- and a4߲-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain a-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain a-neurotoxins and ?-neurotoxins notwithstanding, haditoxin exhibited unique blockade of a7-nAChRs (IC50 180 nm), which is recognized by neither short-chain a-neurotoxins nor ?-neurotoxins. This is the first report of a dimeric short-chain a-neurotoxin interacting with neuronal a7-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent2760807 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationYen_AU
dc.relation.ispartofpagefrom8302en_US
dc.relation.ispartofpageto8315en_US
dc.relation.ispartofissue11en_AU
dc.relation.ispartofjournalJournal of Biological Chemistryen_US
dc.relation.ispartofvolume285en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences not elsewhere classifieden_US
dc.subject.fieldofresearchcode111599en_US
dc.titleStructural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightThis research was originally published in Journal of Biological Chemistry (JBC). Authors, Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra), Journal of Biological Chemistry (JBC) 2010; Vol 285: 8302-8315. Copyright the American Society for Biochemistry and Molecular Biology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitve version.en_AU
gro.date.issued2010
gro.hasfulltextFull Text


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