Article

An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis.

Architecture et Fonction des Macromolécules Biologiques, UMR 6098, CNRS et Universités d'Aix-Marseille I et II, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
Biochemical Journal (impact factor: 4.9). 06/2005; 388(Pt 1):263-71. DOI:10.1042/BJ20041705 pp.263-71
Source: PubMed

ABSTRACT The Om-toxins are short peptides (23-27 amino acids) purified from the venom of the scorpion Opisthacanthus madagascariensis. Their pharmacological targets are thought to be potassium channels. Like Csalpha/beta (cystine-stabilized alpha/beta) toxins, the Om-toxins alter the electrophysiological properties of these channels; however, they do not share any sequence similarity with other scorpion toxins. We herein demonstrate by electrophysiological experiments that Om-toxins decrease the amplitude of the K+ current of the rat channels Kv1.1 and Kv1.2, as well as human Kv1.3. We also determine the solution structure of three of the toxins by use of two-dimensional proton NMR techniques followed by distance geometry and molecular dynamics. The structures of these three peptides display an uncommon fold for ion-channel blockers, Csalpha/alpha (cystine-stabilized alpha-helix-loop-helix), i.e. two alpha-helices connected by a loop and stabilized by two disulphide bridges. We compare the structures obtained and the dipole moments resulting from the electrostatic anisotropy of these peptides with those of the only other toxin known to share the same fold, namely kappa-hefutoxin1.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

alpha-helices
 
dipole moments
 
distance geometry
 
electrophysiological experiments
 
electrophysiological properties
 
K+ current
 
Om-toxins
 
Om-toxins decrease
 
peptides
 
potassium channels
 
rat channels Kv1.1
 
scorpion Opisthacanthus madagascariensis
 
scorpion toxins
 
sequence similarity
 
structures
 
three peptides display
 
toxin
 
toxins
 
two-dimensional proton NMR techniques
 
uncommon