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Bioinformatic characterizations and prediction of K+ and Na+ ion channels effector toxins

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      Abstract

      Background

      K + and Na + channel toxins constitute a large set of polypeptides, which interact with their ion channel targets. These polypeptides are classified in two different structural groups. Recently a new structural group called birtoxin-like appeared to contain both types of toxins has been described. We hypothesized that peptides of this group may contain two conserved structural motifs in K + and/or Na + channels scorpion toxins, allowing these birtoxin-like peptides to be active on K + and/or Na + channels.

      Results

      Four multilevel motifs, overrepresented and specific to each group of K + and/or Na + ion channel toxins have been identified, using GIBBS and MEME and based on a training dataset of 79 sequences judged as representative of K + and Na + toxins.

      Unexpectedly birtoxin-like peptides appeared to present a new structural motif distinct from those present in K + and Na + channels Toxins. This result, supported by previous experimental data, suggests that birtoxin-like peptides may exert their activity on different sites than those targeted by classic K + or Na + toxins.

      Searching, the nr database with these newly identified motifs using MAST, retrieved several sequences (116 with e-value < 1) from various scorpion species (test dataset). The filtering process left 30 new and highly likely ion channel effectors.

      Phylogenetic analysis was used to classify the newly found sequences. Alternatively, classification tree analysis, using CART algorithm adjusted with the training dataset, using the motifs and their 2D structure as explanatory variables, provided a model for prediction of the activity of the new sequences.

      Conclusion

      The phylogenetic results were in perfect agreement with those obtained by the CART algorithm.

      Our results may be used as criteria for a new classification of scorpion toxins based on functional motifs.

      Related collections

      Most cited references 63

      • Record: found
      • Abstract: not found
      • Article: not found

      Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

      The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
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        • Record: found
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        Clustal W and Clustal X version 2.0.

        The Clustal W and Clustal X multiple sequence alignment programs have been completely rewritten in C++. This will facilitate the further development of the alignment algorithms in the future and has allowed proper porting of the programs to the latest versions of Linux, Macintosh and Windows operating systems. The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/
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          • Record: found
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          The neighbor-joining method: a new method for reconstructing phylogenetic trees.

           N Saitou,  M Nei (1987)
          A new method called the neighbor-joining method is proposed for reconstructing phylogenetic trees from evolutionary distance data. The principle of this method is to find pairs of operational taxonomic units (OTUs [= neighbors]) that minimize the total branch length at each stage of clustering of OTUs starting with a starlike tree. The branch lengths as well as the topology of a parsimonious tree can quickly be obtained by using this method. Using computer simulation, we studied the efficiency of this method in obtaining the correct unrooted tree in comparison with that of five other tree-making methods: the unweighted pair group method of analysis, Farris's method, Sattath and Tversky's method, Li's method, and Tateno et al.'s modified Farris method. The new, neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods.
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            Author and article information

            Affiliations
            [1 ]Laboratory of Epidemiology and Ecology of Parasites, Institut Pasteur de Tunis, Tunis, Tunisia
            [2 ]Laboratory of Venom and Toxins, Institut Pasteur de Tunis, Tunis, Tunisia
            [3 ]Research and Teaching Building, Institut Pasteur de Tunis, 13 Place Pasteur, BP 74, 1002 Belvedere-Tunis, Tunisia
            Contributors
            Journal
            BMC Pharmacol
            BMC Pharmacology
            BioMed Central
            1471-2210
            2009
            10 March 2009
            : 9
            : 4
            2660317
            1471-2210-9-4
            19284552
            10.1186/1471-2210-9-4
            Copyright © 2009 Soli et al; licensee BioMed Central Ltd.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Research Article

            Pharmacology & Pharmaceutical medicine

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