Structural Insight into Specificity of Interactions between Nonconventional Three-finger Weak Toxin from Naja kaouthia (WTX) and Muscarinic Acetylcholine Receptors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F15%3A00449347" target="_blank" >RIV/67985823:_____/15:00449347 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1074/jbc.M115.656595" target="_blank" >http://dx.doi.org/10.1074/jbc.M115.656595</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1074/jbc.M115.656595" target="_blank" >10.1074/jbc.M115.656595</a>
Alternative languages
Result language
angličtina
Original language name
Structural Insight into Specificity of Interactions between Nonconventional Three-finger Weak Toxin from Naja kaouthia (WTX) and Muscarinic Acetylcholine Receptors
Original language description
Weak toxin from Naja kaouthia (WTX) belongs to the group of nonconventional ?three-finger snake neurotoxins. It irreversibly inhibits nicotinic acetylcholine receptors and allosterically interacts with muscarinic acetylcholine receptors (mAChRs). Using site-directed mutagenesis, NMR spectroscopy, and computer modeling, we investigated the recombinant mutant WTX analogue (rWTX) which, compared with the native toxin, has an additional N-terminal methionine residue. In comparison with the wild-type toxin,rWTX demonstrated an altered pharmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1- and M2-mAChRs, and increased antagonist binding to M3-mAChR. Positively charged arginine residues located in the flexible loop II were found to be crucial for rWTX interactions with all types of mAChR. Computer modeling suggested that the rWTX loop II protrudes to the M1-mAChR allosteric ligand-binding site blocking the entrance to the orthosteric site. In co
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
ED - Physiology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GA14-05696S" target="_blank" >GA14-05696S: Search of mechanisms responsible for adverse effects of amyloid beta on muscarinic receptor transmission.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
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Volume of the periodical
290
Issue of the periodical within the volume
39
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
23616-23630
UT code for WoS article
000361816500013
EID of the result in the Scopus database
2-s2.0-84942240532