Related Experiment Video
Updated: Sep 20, 2026

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
Solution conformation of alphaA-conotoxin EIVA, a potent neuromuscular nicotinic acetylcholine receptor antagonist
Seung-Wook Chi1, Kyu-Hwan Park, Jae-Eun Suk
1Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
Abstract:
We report the solution three-dimensional structure of an alphaA-conotoxin EIVA determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics. The alphaA-conotoxin EIVA consists of 30 amino acids representing the largest peptide among the alpha/alphaA-family conotoxins discovered so far and targets the neuromuscular nicotinic acetylcholine receptor with high affinity. alphaA-Conotoxin EIVA consists of three distinct structural domains. The first domain is mainly composed of the Cys3-Cys11-disulfide loop and is structurally ill-defined with a large backbone root mean square deviation of 1.91 A. The second domain formed by residues His12-Hyp21 is extremely well defined with a backbone root mean square deviation of 0.52 A, thus forming a sturdy stem for the entire molecule. The third C-terminal domain formed by residues Hyp22-Gly29 shows an intermediate structural order having a backbone root mean square deviation of 1.04 A. A structurally ill-defined N-terminal first loop domain connected to a rigid central molecular stem seems to be the general structural feature of the alphaA-conotoxin subfamily. A detailed structural comparison between alphaA-conotoxin EIVA and alphaA-conotoxin PIVA suggests that the higher receptor affinity of alphaA-conotoxin EIVA than alphaA-conotoxin PIVA might originate from different steric disposition and charge distribution in the second loop "handle" motif.
More Related Videos
10:30A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
07:09Subcutaneous Administration of Muscarinic Antagonists and Triple-Immunostaining of the Levator Auris Longus Muscle in Mice
Published on: September 8, 2011
Related Concept Videos
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Neuromuscular Junction And Blockade
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...