World Library  
Flag as Inappropriate
Email this Article

Maurotoxin

Article Id: WHEBN0007858517
Reproduction Date:

Title: Maurotoxin  
Author: World Heritage Encyclopedia
Language: English
Subject: Scorpio maurus, Ion channel toxins, Beta-Bungarotoxin, Neurotoxins, Onchidal
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Maurotoxin

The protein NMR structure of maurotoxin, illustrating the fluctuations in the protein's native state in solution. The protein backbone is shown in red, the alpha carbons of the eight cysteine residues in green, and the disulfide bridges in yellow. Compare the disulfide bond connectivity to HsTx1 below.
The protein NMR structure of HsTx1, a scorpion toxin with a canonical disulfide bond connectivity.

Maurotoxin (abbreviated MTX) is a peptide toxin from the venom of the Tunisian chactoid scorpion Scorpio maurus palmatus, from which it was first isolated and from which the chemical gets its name. It acts by blocking several types of voltage-gated potassium channel.

Contents

  • Chemistry 1
  • Target 2
  • Mode of action 3
  • References 4

Chemistry

Maurotoxin is a peptide of 34 cysteine residues may be mediated by the presence of adjacent prolines. The peptide contains an alpha helix linked by two disulfide bridges to a two-stranded antiparallel beta sheet.

Target

Scorpion toxins constitute the largest group of potassium (K+) channel blockers and are useful pharmacological probes to investigate ion channels and their functions.

Maurotoxin (MTX) blocks various K+ -channels:

The structural and pharmacological features of MTX suggest that MTX belongs to a new class of natural K+ channel blockers structurally intermediate between the Na+ (60–70 residues and four disulfide bridges) and K+ channel scorpion toxin families (less than 40 residues and three disulfide bridges).

The intermediate conductance Ca2+-activated K+ (IK) channel is present in peripheral tissues, including secretory epithelia and blood cells. An important physiological role of the IK channel is to help maintain large electrical gradients for the sustained transport of ions such as Ca2+ that controls T lymphocyte (T cell) proliferation. Thus IK blockers could be potential immunosuppressants for the treatment of autoimmune disorders (such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis).

Mode of action

MTX occludes the pore region of various potassium channels (Kv1.2, IKCa1, Kv1.3) by establishing strong interactions between its lysine-23 residue and the glycine-tyrosine-glycine-aspartate (GYGD) motif of the channel. MTX thus blocks the channels by binding in the external vestibule of the pore to block the ion conduction pathway. Although Kv1.1, Kv1.2, and Kv1.3 have a very similar pore structure, they display different pharmacological sensitivity to MTX.

References

  1. Carlier, E., et al., Effect of maurotoxin, a four disulfide-bridged toxin from the chactoid scorpion Scorpio maurus, on Shaker K+ channels. J Pept Res, 2000. 55(6): p. 419-27.
  2. Castle, N.A., et al., Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol Pharmacol, 2003. 63(2): p. 409-18.
  3. Fu, W., et al., Brownian dynamics simulations of the recognition of the scorpion toxin maurotoxin with the voltage-gated potassium ion channels. Biophys J, 2002. 83(5): p. 2370-85.
  4. Jensen, B.S., et al., The Ca2+-activated K+ channel of intermediate conductance:a possible target for immune suppression. Expert Opin Ther Targets, 2002. 6(6): p. 623-36.
  5. Kharrat, R., et al., Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels. Eur J Biochem, 1996. 242(3): p. 491-8.
  6. M'Barek, S., et al., A maurotoxin with constrained standard disulfide bridging: innovative strategy of chemical synthesis, pharmacology, and docking on K+ channels. J Biol Chem, 2003. 278(33): p. 31095-104.
  7. Rochat, H., et al., Maurotoxin, a four disulfide bridges scorpion toxin acting on K+ channels. Toxicon, 1998. 36(11): p. 1609-11.
  8. Visan, V., et al., Mapping of maurotoxin binding sites on hKv1.2, hKv1.3, and hIKCa1 channels. Mol Pharmacol, 2004. 66(5): p. 1103-12.
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.