ArticleProceedings of the National Academy of Sciences of the United States of America2008
Atypical nicotinic agonist bound conformations conferring subtype selectivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 85 citations in OpenAlex.
- Effects of dinotefuran and its metabolites on the early life stage development of medaka (Toxicology reports · 2026Article
- Functional Expression of Nicotinic Receptors on iPSC-Derived Astrocytes and Signalling Disturbances by a Panel of Neonicotinoid Pesticides and Their Metabolites.International journal of molecular sciences · 2026Article
- Discovery and biological characterization of a novel mesoionic insecticide fenmezoditiaz.Pest management science · 2025Article
- Protein Painting Mass Spectrometry in the Discovery of Interaction Sites within the Acetylcholine Binding Protein.ACS chemical neuroscience · 2024Article
- Structural Insights into Neonicotinoids and N-Unsubstituted Metabolites on Human nAChRs by Molecular Docking, Dynamics Simulations, and Calcium Imaging.International journal of molecular sciences · 2023Article
- Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case.Molecules (Basel, Switzerland) · 2021Article
- Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons.Archives of toxicology · 2021Article
- Review
- Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity.Frontiers in immunology · 2021Review
- Modality-specific impairment of learning by a neonicotinoid pesticide.Biology letters · 2019Article
- Molecular recognition of thiaclopride by Aplysia californica AChBP: new insights from a computational investigation.Journal of computer-aided molecular design · 2015Article
- Insight into the Binding Mode of Agonists of the Nicotinic Acetylcholine Receptor from Calculated Electron Densities.Chemphyschem : a European journal of chemical physics and physical chemistry · 2015Article
- Effects of neonicotinoids and fipronil on non-target invertebrates.Environmental science and pollution research international · 2015Review
- Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.Environmental science and pollution research international · 2015Review
- The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae).Journal of insect science (Online) · 2015Article
- Insect nicotinic receptor interactions in vivo with neonicotinoid, organophosphorus, and methylcarbamate insecticides and a synergist.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Synthesis, insecticidal, and antibacterial activities of novel neonicotinoid analogs with dihydropyridine.Chemistry Central journal · 2013Article
- Size matters in activation/inhibition of ligand-gated ion channels.Trends in pharmacological sciences · 2012Review
- Structural determinants of imidacloprid-based nicotinic acetylcholine receptor inhibitors identified using 3D-QSAR, docking and molecular dynamics.Journal of molecular modeling · 2012Article
- [(3)H]Epibatidine photolabels non-equivalent amino acids in the agonist binding site of Torpedo and alpha4beta2 nicotinic acetylcholine receptors.The Journal of biological chemistry · 2009Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The nicotinic acetylcholine (ACh) receptor (nAChR) plays a crucial role in excitatory neurotransmission and is an important target for drugs and insecticides. Diverse nAChR subtypes with various subunit combinations confer differential selectivity for nicotinic drugs. We investigated the subtype selectivity of nAChR agonists by comparing two ACh-binding proteins (AChBPs) as structural surrogates with distinct pharmacological profiles [i.e., Lymnaea stagnalis (Ls) AChBP of low neonicotinoid and high nicotinoid sensitivities and Aplysia californica (Ac) AChBP of high neonicotinoid sensitivity] mimicking vertebrate and insect nAChR subtypes, respectively. The structural basis of subtype selectivity was examined here by photoaffinity labeling. Two azidoneonicotinoid probes in the Ls-AChBP surprisingly modified two distinct and distant subunit interface sites: loop F Y164 of the complementary or (-)-face subunit and loop C Y192 of the principal or (+)-face subunit, whereas three azidonicotinoid probes derivatized only Y192. Both the neonicotinoid and nicotinoid probes labeled Ac-AChBP at only one position at the interface between loop C Y195 and loop E M116. These findings were used to establish structural models of the two AChBP subtypes. In the Ac-AChBP, the neonicotinoids and nicotinoids are nestled in similar bound conformations. Intriguingly, for the Ls-AChBP, the neonicotinoids have two bound conformations that are inverted relative to each other, whereas nicotinoids appear buried in only one conserved conformation as seen for the Ac-AChBP subtype. Accordingly, the subtype selectivity is based on two disparate bound conformations of nicotinic agonists, thereby establishing an atypical concept for neonicotinoid versus nicotinoid selectivity between insect and vertebrate nAChRs.
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