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      Molecular Characterization and Biodiversity of a Putative Chlorotoxin from the Iranian Yellow Scorpion Odontobuthus doriae

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          Abstract

          Background:

          Chloride channels have already been over-expressed in the different types of cancer. Chlorotoxins, as the blocking agent of these channels, have been indicated to be an effective drug against tumors. In this study, we characterized a putative chlorotoxin from a cDNA library of the venom glands obtained from the Iranian scorpion Odontobuthus doriae.

          Methods:

          A cDNA library was constructed from venom gland transcriptome of six scorpions. The cDNA encoding Odontobuthus doriae chlorotoxin was isolated from the library, and its putative peptide was characterized by some bioinformatics software such as protein blast, SignalP4.0, DISULFIND and Clustal Omega.

          Results:

          The mature Odontobuthus doriae chlorotoxin peptide has a 35-amino-acid residue and four disulfide bounds. This putative chlorotoxin is a small, compact, and stable molecule. Moreover, based on the open reading frame sequence similarity, this peptide is similar to Buthus martensii Karsch chlorotoxin-like toxin and Bm12-b neurotoxins from the Chinese scorpion Mesobuthus martensii.

          Conclusion:

          The small size of this putative chlorotoxin and its stability make it as a suitable candidate for medical and pharmacological research, especially in the cancer research.

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          Most cited references18

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          DISULFIND: a disulfide bonding state and cysteine connectivity prediction server

          DISULFIND is a server for predicting the disulfide bonding state of cysteines and their disulfide connectivity starting from sequence alone. Optionally, disulfide connectivity can be predicted from sequence and a bonding state assignment given as input. The output is a simple visualization of the assigned bonding state (with confidence degrees) and the most likely connectivity patterns. The server is available at .
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            Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2.

            Primary brain tumors (gliomas) have the unusual ability to diffusely infiltrate the normal brain thereby evading surgical treatment. Chlorotoxin is a scorpion toxin that specifically binds to the surface of glioma cells and impairs their ability to invade. Using a recombinant His-Cltx we isolated and identified the principal Cltx receptor on the surface of glioma cells as matrix metalloproteinase-2 (MMP-2). MMP-2 is specifically up-regulated in gliomas and related cancers, but is not normally expressed in brain. We demonstrate that Cltx specifically and selectively interacts with MMP-2 isoforms, but not with MMP-1, -3, and -9, which are also expressed in malignant glioma cells. Importantly, we show that the anti-invasive effect of Cltx on glioma cells can be explained by its interactions with MMP-2. Cltx exerts a dual effect on MMP-2: it inhibits the enzymatic activity of MMP-2 and causes a reduction in the surface expression of MMP-2. These findings suggest that Cltx is a specific MMP-2 inhibitor with significant therapeutic potential for gliomas and other diseases that invoke the activity of MMP-2.
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              Scorpion venom components that affect ion-channels function.

              The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na(+)-, K(+)- and Ca(++)-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are nowadays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na(+)-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K(+)-channels are normally pore blocking agents. The Ryanodine Ca(++)-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Iran Biomed J
                Iran. Biomed. J
                Iranian Biomedical Journal
                Pasteur Institute (Iran )
                1028-852X
                2008-823X
                September 2017
                : 21
                : 5
                : 342-346
                Affiliations
                [1 ]Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
                [2 ]Department of Pharmacology and Toxicology, School of Pharmacy and Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                Author notes
                Corresponding Author: Hamid Galehdari Faculty of Science, Shahid Chamran University, Ahvaz, Iran. Tel.: (+98-61) 33338965; E-mail: galehdari187@ 123456yahoo.com
                Article
                IBJ-21-342
                10.18869/acadpub.ibj.21.5.342
                5548967
                c25198dd-5517-4571-bef3-40bb8ae86166
                Copyright: © Iranian Biomedical Journal

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 July 2016
                : 18 July 2016
                : 26 July 2016
                Categories
                Short Communication

                chlorotoxin,scorpion,odontobuthus doriae,cdna library
                chlorotoxin, scorpion, odontobuthus doriae, cdna library

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