Source:http://linkedlifedata.com/resource/pubmed/id/16309623
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2005-12-26
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| pubmed:databankReference | |
| pubmed:abstractText |
Scorpion venoms are among the most widely known source of peptidyl neurotoxins used for callipering different ion channels, e.g., for Na(+), K(+), Ca(+) or Cl(-). An alpha-toxin (Bs-Tx28) has been purified from the venom of scorpion Buthus sindicus, a common yellow scorpion of Sindh, Pakistan. The primary structure of Bs-Tx28 was established using a combination of MALDI-TOF-MS, LC-ESI-MS, and automated Edman degradation analysis. Bs-Tx28 consists of 65 amino acid residues (7274.3+/-2Da), including eight cysteine residues, and shows very high sequence identity (82-94%) with other long-chain alpha-neurotoxins, active against receptor site-3 of mammalian (e.g., Lqq-IV and Lqh-IV from scorpions Leiurus sp.) and insect (e.g., BJalpha-IT and Od-1 from Buthotus judaicus and Odonthobuthus doriae, respectively) voltage-gated Na(+) channels. Multiple sequence alignment and phylogenetic analysis of Bs-Tx28 with other known alpha- and alpha-like toxins suggests the presence of a new and separate subfamily of scorpion alpha-toxins. Bs-Tx28 which is weakly active in both, mammals and insects (LD(50) 0.088 and 14.3microg/g, respectively), shows strong induction of the rat afferent nerve discharge in a dose-dependent fashion (EC(50)=0.01microg/mL) which was completely abolished in the presence of tetrodotoxin suggesting the binding of Bs-Tx28 to the TTX-sensitive Na(+)-channel. Three-dimensional structural features of Bs-Tx28, established by homology modeling, were compared with other known classical alpha-mammal (AaH-II), alpha-insect (Lqh-alphaIT), and alpha-like (BmK-M4) toxins and revealed subtle variations in the Nt-, Core-, and RT-CT-domains (functional domains) which constitute a "necklace-like" structure differing significantly in all alpha-toxin subfamilies. On the other hand, a high level of conservation has been observed in the conserved hydrophobic surface with the only substitution of W43 (Y43/42) and an additional hydrophobic character at position F40 (L40/A/V/G39), as compared to the other mentioned alpha-toxins. Despite major differences within the primary structure and activities of Bs-Tx28, it shares a common structural and functional motif (e.g., transRT-farCT) within the RT-CT domain which is characteristic of scorpion alpha-mammal toxins.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0003-9861
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
445
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
81-94
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16309623-Action Potentials,
pubmed-meshheading:16309623-Amino Acid Sequence,
pubmed-meshheading:16309623-Animals,
pubmed-meshheading:16309623-Blattellidae,
pubmed-meshheading:16309623-Circular Dichroism,
pubmed-meshheading:16309623-Gastrointestinal Motility,
pubmed-meshheading:16309623-Jejunum,
pubmed-meshheading:16309623-Lethal Dose 50,
pubmed-meshheading:16309623-Mesenteric Arteries,
pubmed-meshheading:16309623-Mice,
pubmed-meshheading:16309623-Models, Molecular,
pubmed-meshheading:16309623-Molecular Sequence Data,
pubmed-meshheading:16309623-Neurotoxins,
pubmed-meshheading:16309623-Phylogeny,
pubmed-meshheading:16309623-Protein Conformation,
pubmed-meshheading:16309623-Rats,
pubmed-meshheading:16309623-Rats, Sprague-Dawley,
pubmed-meshheading:16309623-Scorpion Venoms,
pubmed-meshheading:16309623-Sequence Alignment,
pubmed-meshheading:16309623-Sequence Homology, Amino Acid,
pubmed-meshheading:16309623-Sodium Channel Blockers,
pubmed-meshheading:16309623-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:16309623-Structure-Activity Relationship,
pubmed-meshheading:16309623-Tetrodotoxin
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| pubmed:year |
2006
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| pubmed:articleTitle |
Structure-activity relationship of an alpha-toxin Bs-Tx28 from scorpion (Buthus sindicus) venom suggests a new alpha-toxin subfamily.
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| pubmed:affiliation |
International Center for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan. syedabid_ali@yahoo.com
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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