dc.contributor.author | Roy, Amrita | |
dc.contributor.author | Zhou, Xingding | |
dc.contributor.author | Chong, Ming Zhi | |
dc.contributor.author | D'hoedt, Dieter | |
dc.contributor.author | Foo, Chun Shin | |
dc.contributor.author | Rajagopalan, Nandhakishore | |
dc.contributor.author | Nirthanan, Selvanayagam | |
dc.contributor.author | Bertrand, Daniel | |
dc.contributor.author | Sivaraman, J | |
dc.contributor.author | Kini, R Manjunatha | |
dc.date.accessioned | 2017-05-03T15:29:00Z | |
dc.date.available | 2017-05-03T15:29:00Z | |
dc.date.issued | 2010 | |
dc.date.modified | 2010-10-07T04:07:18Z | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.doi | 10.1074/jbc.M109.074161 | |
dc.identifier.uri | http://hdl.handle.net/10072/34020 | |
dc.description.abstract | Snake 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.format.extent | 2760807 bytes | |
dc.format.mimetype | application/pdf | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Society for Biochemistry and Molecular Biology | |
dc.publisher.place | United States | |
dc.relation.ispartofstudentpublication | Y | |
dc.relation.ispartofpagefrom | 8302 | |
dc.relation.ispartofpageto | 8315 | |
dc.relation.ispartofissue | 11 | |
dc.relation.ispartofjournal | Journal of Biological Chemistry | |
dc.relation.ispartofvolume | 285 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Chemical sciences | |
dc.subject.fieldofresearch | Biological sciences | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences not elsewhere classified | |
dc.subject.fieldofresearchcode | 34 | |
dc.subject.fieldofresearchcode | 31 | |
dc.subject.fieldofresearchcode | 32 | |
dc.subject.fieldofresearchcode | 321499 | |
dc.title | Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra) | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.rights.copyright | This 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.issued | 2010 | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Nirthanan, Niru | |