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
| Autor: | Li-Sam Cheah, Ponnampalam Gopalakrishnakone, R. Manjunatha Kini, Hoon Eng Khoo, Daniel Bertrand, Matthew C.E. Gwee, Eric Charpantier, Selvanayagam Nirthanan |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Bungarus Magnetic Resonance Spectroscopy Molecular Sequence Data Nicotinic Antagonists Receptors Nicotinic medicine.disease_cause Biochemistry Bungarus candidus medicine Animals Amino Acid Sequence Receptor Molecular Biology Chromatography High Pressure Liquid Acetylcholine receptor Neurons Neuromuscular Blockade biology Cytotoxins Toxin Chemistry Muscles Antagonist Cell Biology Evoked Potentials Motor biology.organism_classification Acetylcholine Rats Electrophysiology Nicotinic agonist medicine.anatomical_structure nervous system Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Peripheral nervous system Biophysics Snake Venoms |
| Zdroj: | Journal of Biological Chemistry. 277:17811-17820 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111152200 |
| Popis: | 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 postjunctional neuromuscular blockade that was readily and completely reversible. Nanomolar concentrations of candoxin (IC(50) = approximately 10 nm) also blocked acetylcholine-evoked currents in oocyte-expressed rat muscle (alphabetagammadelta) nicotinic acetylcholine receptors in a reversible manner. In contrast, it produced a poorly reversible block (IC(50) = approximately 50 nm) of rat neuronal alpha7 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 alpha7 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 (alphabetagammadelta) and long chain neurotoxins to alpha7 receptors. Candoxin is therefore a novel toxin that shares a common scaffold with long chain alpha-neurotoxins but possibly utilizes additional functional determinants that assist in recognizing neuronal alpha7 receptors. |
| Databáze: | OpenAIRE |
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