Abstract
α9α10 nicotinic acetylcholine receptors (nAChRs) putatively exist at different stoichiometries. We systematically investigated the molecular determinants of α-conotoxins Vc1.1, RgIA#, and PeIA inhibition at hypothetical stoichiometries of the human α9α10 nAChR. Our results suggest that only Vc1.1 exhibits stoichiometric-dependent inhibition at the α9α10 nAChR. The hydrogen bond between N154 of α9 and D11 of Vc1.1 at the α9(+)-α9(-) interface is responsible for the stoichiometric-dependent potency of Vc1.1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Conotoxins / chemistry*
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Conotoxins / pharmacology*
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Humans
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Models, Molecular
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Molecular Dynamics Simulation
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Molecular Structure
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Nicotinic Antagonists / chemistry
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Nicotinic Antagonists / pharmacology
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Oocytes / cytology
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Oocytes / drug effects*
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Oocytes / metabolism
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Protein Conformation
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Protein Subunits
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Receptors, Nicotinic / chemistry*
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Receptors, Nicotinic / classification
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Receptors, Nicotinic / metabolism*
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Xenopus laevis
Substances
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Conotoxins
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Nicotinic Antagonists
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Protein Subunits
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Receptors, Nicotinic
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alpha-conotoxin Vc1.1