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|Title:||Candoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (αβγδ) but a poorly reversible antagonist of neuronal α7 nicotinic acetylcholine receptors||Authors:||Nirthanan, S.
Manjunatha Kini, R.
|Issue Date:||17-May-2002||Citation:||Nirthanan, S., Charpantier, E., Gopalakrishnakone, P., Gwee, M.C.E., Khoo, H.-E., Cheah, L.-S., Bertrand, D., Manjunatha Kini, R. (2002-05-17). Candoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (αβγδ) but a poorly reversible antagonist of neuronal α7 nicotinic acetylcholine receptors. Journal of Biological Chemistry 277 (20) : 17811-17820. ScholarBank@NUS Repository.||Abstract:||In contrast to most short and long chain curaremimetic neurotoxins that produce virtually irreversible neuromuscular blockade in isolated nerve-muscle preparations, candoxin, a novel three-finger toxin from the Malayan krait Bungarus candidus, produced post-junctional neuromuscular blockade that was readily and completely reversible. Nanomolar concentrations of candoxin (IC50 = ∼10 nM) also blocked acetylcholine-evoked currents in oocyte-expressed rat muscle (αβγδ) nicotinic acetylcholine receptors in a reversible manner. In contrast, it produced a poorly reversible block (IC50 = ∼50 nM) of rat neuronal α7 receptors, clearly showing diverse functional profiles for the two nicotinic receptor subsets. Interestingly, candoxin lacks the helix-like segment cyclized by the fifth disulfide bridge at the tip of the middle loop of long chain neurotoxins, reported to be critical for binding to α7 receptors. However, its solution NMR structure showed the presence of some functionally invariant residues involved in the interaction of both short and long chain neurotoxins to muscle (αβγδ) and long chain neurotoxins to α7 receptors. Candoxin is therefore a novel toxin that shares a common scaffold with long chain α-neurotoxins but possibly utilizes additional functional determinants that assist in recognizing neuronal α7 receptors.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/100212||ISSN:||00219258|
|Appears in Collections:||Staff Publications|
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