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dc.contributor.authorNirthanan, S
dc.date.accessioned2020-08-07T04:50:20Z
dc.date.available2020-08-07T04:50:20Z
dc.date.issued2020
dc.identifier.issn0006-2952
dc.identifier.doi10.1016/j.bcp.2020.114168
dc.identifier.urihttp://hdl.handle.net/10072/396334
dc.description.abstractSnake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane receptors and ion channels. This included the localisation, isolation and characterization of the first receptor (nAChR); and by extension, the pathophysiology and pharmacology of neuromuscular transmission and associated pathologies such as myasthenia gravis, as well as our understanding of the role of α-3FNTxs in snakebite envenomation leading to novel concepts of targeted treatment. Subsequent studies on a variety of animal venoms have yielded a plethora of novel toxins that have revolutionized molecular biomedicine and advanced drug discovery from bench to bedside. This review provides an overview of nAChRs and their subtypes, classification of α-3FNTxs and the challenges of typifying an increasing arsenal of structurally and functionally unique toxins, and the three-finger protein (3FP) fold in the context of the uPAR/Ly6/CD59/snake toxin superfamily. The pharmacology of snake α-3FNTxs including their mechanisms of neuromuscular blockade, variations in reversibility of nAChR interactions, specificity for nAChR subtypes or for distinct ligand-binding interfaces within a subtype and the role of α-3FNTxs in neurotoxic envenomation are also detailed. Lastly, a reconciliation of structure-function relationships between α-3FNTx and nAChRs, derived from historical mutational and biochemical studies and emerging atomic level structures of nAChR models in complex with α-3FNTxs is discussed.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofjournalBiochem Pharmacol
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3214
dc.subject.keywordsα-neurotoxins | snake three-finger toxin | snakebite envenomation | nicotinic acetylcholine receptor | cholinergic neurotransmission | protein structure-function
dc.titleSnake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationNirthanan, S, Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine., Biochem Pharmacol, 2020
dcterms.dateAccepted2020-07-20
dc.date.updated2020-08-07T04:10:21Z
gro.description.notepublicThis publication has been entered in Griffith Research Online as an advanced online version.
gro.hasfulltextNo Full Text
gro.griffith.authorNirthanan, Niru


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