Show simple item record

dc.contributor.authorRoy, Amrita
dc.contributor.authorZhou, Xingding
dc.contributor.authorChong, Ming Zhi
dc.contributor.authorD'hoedt, Dieter
dc.contributor.authorFoo, Chun Shin
dc.contributor.authorRajagopalan, Nandhakishore
dc.contributor.authorNirthanan, Selvanayagam
dc.contributor.authorBertrand, Daniel
dc.contributor.authorSivaraman, J
dc.contributor.authorKini, R Manjunatha
dc.date.accessioned2017-05-03T15:29:00Z
dc.date.available2017-05-03T15:29:00Z
dc.date.issued2010
dc.date.modified2010-10-07T04:07:18Z
dc.identifier.issn0021-9258
dc.identifier.doi10.1074/jbc.M109.074161
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent2760807 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationY
dc.relation.ispartofpagefrom8302
dc.relation.ispartofpageto8315
dc.relation.ispartofissue11
dc.relation.ispartofjournalJournal of Biological Chemistry
dc.relation.ispartofvolume285
dc.rights.retentionY
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences not elsewhere classified
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode321499
dc.titleStructural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
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.
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorNirthanan, Niru


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record