Research article summary (published 30 Apr 2002):

Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels.

Full Abstract

Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX-resistant VSSC current in sensory ganglion neurons. In rat brain neurons, these peptides preferentially inhibited the persistent over the transient VSSC current. Radioligand binding assays revealed that PIIIA, PIIIA-(2-22), and mu-conotoxins GIIIB discriminated among TTX-sensitive VSSCs in rat brain, that these and GIIIC discriminated among the corresponding VSSCs in human brain, and GIIIA had low affinity for neuronal VSSCs. (1)H NMR studies found that PIIIA adopts two conformations in solution due to cis/trans isomerization at hydroxyproline 8. The major trans conformation results in a three-dimensional structure that is significantly different from the previously identified conformation of mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by mu-conotoxins.

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Author information

Author/s: Nielsen, Katherine J (KJ); Watson, Michael (M); Adams, David J (DJ); Hammarström, Anna K (AK); Gage, Peter W (PW); Hill, Justine M (JM); Craik, David J (DJ); Thomas, Linda (L); Adams, Denise (D); Alewood, Paul F (PF); Lewis, Richard J (RJ);

Affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of biological chemistry (J Biol Chem), published in United States. (Language: eng)

Reference: 2002-Jul; vol 277 (issue 30) : pp 27247-55

Dates: Created 2002/07/22; Completed 2002/08/22; Revised 2006/11/15;

PMID: 12006587, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amino Acid Sequence Animals Brain - drug effects; metabolism Conotoxins - chemistry Dose-Response Relationship, Drug Electrophysiology Hippocampus - metabolism Humans Inhibitory Concentration 50 Magnetic Resonance Spectroscopy Models, Molecular

Models, Molecular Molecular Sequence Data Muscle, Skeletal - drug effects; metabolism Neurons - metabolism Peptide Biosynthesis Protein Conformation Radioligand Assay Rats Sodium Channels - chemistry Tetrodotoxin - pharmacology Time Factors

Associated Chemicals: Conotoxins (0) ; Sodium Channels (0) ; mu-conotoxin PIIIA (0) ; Tetrodotoxin (4368-28-9)

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