Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00474008" target="_blank" >RIV/67985823:_____/17:00474008 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/srep40381" target="_blank" >http://dx.doi.org/10.1038/srep40381</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/srep40381" target="_blank" >10.1038/srep40381</a>

Result language
angličtina
Original language name
Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors
Original language description
Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane a-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding. The affinity of NMS at the allosteric site is in the micromolar range for all receptor subtypes. Using molecular modelling of the M2 receptor we found that E172 and E175 in the second extracellular loop and N419 in the third extracellular loop are involved in allosteric binding of NMS. Mutation of these amino acids to alanine decreased affinity of NMS for the allosteric binding site confirming results of molecular modelling. The allosteric binding site of NMS overlaps with the binding site of some allosteric, ectopic and bitopic ligands. Understanding of interactions of NMS at the allosteric binding site is essential for correct analysis of binding and action of these ligands.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)

Project
<a href="/en/project/GBP304%2F12%2FG069" target="_blank" >GBP304/12/G069: Project of excellence in the field of neuroscience</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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