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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
1993-4-23
|
| pubmed:abstractText |
The venom of the scorpion Androctonus mauretanicus mauretanicus contains a toxin, P05, which is structurally and functionally similar to scorpion leiurotoxin I (87% sequence identity), a blocker of the apamin-sensitive Ca(2+)-activated K+ channels. It is a 31-residue polypeptide cross-linked by three disulfide bridges. A C-terminal carboxyl-amidated analog of P05 (sP05-NH2) was chemically synthesized by the solid-phase technique and fully characterized. Toxicity assays in vivo established that sP05-NH2, like native P05, is a potent and lethal neurotoxic agent in mice (LD50 of 20 ng per mouse). Pharmacological assays in vitro however showed that, unlike P05 which has a binding affinity of 2 x 10(-11) M, sP05-NH2 apparently binds irreversibly to the apamin receptor. Iodination at the C-terminal His gave diiodo-sP05-NH2, which had a binding affinity similar to that of native P05. The disulfide bridge pairings were chemically determined for sP05-NH2 and thereby deduced for P05 and leiurotoxin I: linkages were between Cys3 and Cys21, Cys8 and Cys26, and Cys12 and Cys28. Molecular dynamics refinement of P05 also using data from leiurotoxin I suggests that P05 is mainly composed of a double-stranded, antiparallel beta-sheet (from Leu18 to Val29) linked to an alpha-helix (from Arg6 to Gly16) by two disulfides (Cys8-Cys26 and Cys12-Cys28) and to an extended fragment (from Thr1 to Leu5) by the third disulfide (Cys3-Cys21). In agreement with the model, circular dichroism analysis of sP05-NH2 showed that the toxin structure is highly rigid.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apamin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Scorpion Venoms
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0006-2960
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
23
|
| pubmed:volume |
32
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2763-70
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8457543-Amino Acid Sequence,
pubmed-meshheading:8457543-Animals,
pubmed-meshheading:8457543-Apamin,
pubmed-meshheading:8457543-Binding, Competitive,
pubmed-meshheading:8457543-Brain,
pubmed-meshheading:8457543-Calcium,
pubmed-meshheading:8457543-Circular Dichroism,
pubmed-meshheading:8457543-Indicators and Reagents,
pubmed-meshheading:8457543-Kinetics,
pubmed-meshheading:8457543-Lethal Dose 50,
pubmed-meshheading:8457543-Mice,
pubmed-meshheading:8457543-Models, Molecular,
pubmed-meshheading:8457543-Molecular Sequence Data,
pubmed-meshheading:8457543-Neurotoxins,
pubmed-meshheading:8457543-Potassium Channels,
pubmed-meshheading:8457543-Protein Conformation,
pubmed-meshheading:8457543-Rats,
pubmed-meshheading:8457543-Scorpion Venoms,
pubmed-meshheading:8457543-Structure-Activity Relationship,
pubmed-meshheading:8457543-Synaptosomes
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
P05, a new leiurotoxin I-like scorpion toxin: synthesis and structure-activity relationships of the alpha-amidated analog, a ligand of Ca(2+)-activated K+ channels with increased affinity.
|
| pubmed:affiliation |
Laboratoire de Biochimie, CNRS URA 1455, Faculté de Médecine Nord, Marseille, France.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|