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Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins

Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Con...

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Autores principales: Kudryavtsev, Denis, Shelukhina, Irina, Vulfius, Catherine, Makarieva, Tatyana, Stonik, Valentin, Zhmak, Maxim, Ivanov, Igor, Kasheverov, Igor, Utkin, Yuri, Tsetlin, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448168/
https://www.ncbi.nlm.nih.gov/pubmed/26008231
http://dx.doi.org/10.3390/toxins7051683
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author Kudryavtsev, Denis
Shelukhina, Irina
Vulfius, Catherine
Makarieva, Tatyana
Stonik, Valentin
Zhmak, Maxim
Ivanov, Igor
Kasheverov, Igor
Utkin, Yuri
Tsetlin, Victor
author_facet Kudryavtsev, Denis
Shelukhina, Irina
Vulfius, Catherine
Makarieva, Tatyana
Stonik, Valentin
Zhmak, Maxim
Ivanov, Igor
Kasheverov, Igor
Utkin, Yuri
Tsetlin, Victor
author_sort Kudryavtsev, Denis
collection PubMed
description Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A(2) were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds.
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spelling pubmed-44481682015-06-01 Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins Kudryavtsev, Denis Shelukhina, Irina Vulfius, Catherine Makarieva, Tatyana Stonik, Valentin Zhmak, Maxim Ivanov, Igor Kasheverov, Igor Utkin, Yuri Tsetlin, Victor Toxins (Basel) Review Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A(2) were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds. MDPI 2015-05-14 /pmc/articles/PMC4448168/ /pubmed/26008231 http://dx.doi.org/10.3390/toxins7051683 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kudryavtsev, Denis
Shelukhina, Irina
Vulfius, Catherine
Makarieva, Tatyana
Stonik, Valentin
Zhmak, Maxim
Ivanov, Igor
Kasheverov, Igor
Utkin, Yuri
Tsetlin, Victor
Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title_full Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title_fullStr Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title_full_unstemmed Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title_short Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins
title_sort natural compounds interacting with nicotinic acetylcholine receptors: from low-molecular weight ones to peptides and proteins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448168/
https://www.ncbi.nlm.nih.gov/pubmed/26008231
http://dx.doi.org/10.3390/toxins7051683
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