dc.contributor.author | Nirthanan, S | |
dc.date.accessioned | 2020-08-07T04:50:20Z | |
dc.date.available | 2020-08-07T04:50:20Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 0006-2952 | |
dc.identifier.doi | 10.1016/j.bcp.2020.114168 | |
dc.identifier.uri | http://hdl.handle.net/10072/396334 | |
dc.description.abstract | Snake 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofjournal | Biochem Pharmacol | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.subject.keywords | α-neurotoxins | snake three-finger toxin | snakebite envenomation | nicotinic acetylcholine receptor | cholinergic neurotransmission | protein structure-function | |
dc.title | Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine. | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Nirthanan, S, Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine., Biochem Pharmacol, 2020 | |
dcterms.dateAccepted | 2020-07-20 | |
dc.date.updated | 2020-08-07T04:10:21Z | |
gro.description.notepublic | This publication has been entered in Griffith Research Online as an advanced online version. | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Nirthanan, Niru | |