ReviewBiochemical pharmacology2007
Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes.
Review in Biochemical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails.Marine drugs · 2018Review
- Structural mechanisms for α-conotoxin activity at the human α3β4 nicotinic acetylcholine receptor.Scientific reports · 2017Article
- Trapping of ivermectin by a pentameric ligand-gated ion channel upon open-to-closed isomerization.Scientific reports · 2017Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Escherichia coli Protein Expression System for Acetylcholine Binding Proteins (AChBPs).PloS one · 2016Article
- Efficient expression of acetylcholine-binding protein from Aplysia californica in Bac-to-Bac system.BioMed research international · 2014Article
- Complex between α-bungarotoxin and an α7 nicotinic receptor ligand-binding domain chimaera.The Biochemical journal · 2013Article
- Inter-residue coupling contributes to high-affinity subtype-selective binding of α-bungarotoxin to nicotinic receptors.The Biochemical journal · 2013Article
- Defining the putative inhibitory site for a selective negative allosteric modulator of human α4β2 neuronal nicotinic receptors.ACS chemical neuroscience · 2012Article
- Molecular dissection of Cl--selective Cys-loop receptor points to components that are dispensable or essential for channel activity.The Journal of biological chemistry · 2011Article
- Creating an α7 nicotinic acetylcholine recognition domain from the acetylcholine-binding protein: crystallographic and ligand selectivity analyses.The Journal of biological chemistry · 2011Article
- Expeditious synthesis ofTetrahedron letters · 2011Article
- Conformational selection or induced fit? 50 years of debate resolved.F1000 biology reports · 2011Article
- Probing pore constriction in a ligand-gated ion channel by trapping a metal ion in the pore upon agonist dissociation.The Journal of biological chemistry · 2010Article
- Nicotinic pharmacophore: the pyridine N of nicotine and carbonyl of acetylcholine hydrogen bond across a subunit interface to a backbone NH.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system.Nature reviews. Drug discovery · 2009Review
- A virtual screening study of the acetylcholine binding protein using a relaxed-complex approach.Computational biology and chemistry · 2009Article
- Homology modeling and dynamics of the extracellular domain of rat and human neuronal nicotinic acetylcholine receptor subtypes alpha4beta2 and alpha7.Journal of molecular modeling · 2008Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Neuronal nicotinic receptors, encoded by nine genes of the alpha and three of the beta type of subunits, and whose gene products assemble in distinct permutations as pentameric molecules, constitute a fertile area for structure-guided drug design. Design strategies are augmented by a wide variety of peptide, alkaloid and terpenoid toxins from various marine and terrestrial species that interact with nicotinic receptors. Also, acetylcholine-binding proteins from mollusks, as structural surrogates of the receptor that mimic its extracellular domain, provide atomic resolution templates for analysis of structure and response. Herein, we describe a structure-guided approach to nicotinic ligand design that employs crystallography of this protein as the basic template, but also takes into consideration the dynamic properties of the receptor molecules in their biological media. We present the crystallographic structures of several complexes of various agonists and antagonists that associate with the agonist site and can competitively block the action of acetylcholine. In so far as the extracellular domain is involved, we identify additional non-competitive sites at those subunit interfaces where agonists do not preferentially bind. Ligand association at these interface sites may modulate receptor function. Ligand binding is also shown by solution-based spectroscopic and spectrometric methods to affect the dynamics of discrete domains of the receptor molecule. The surrogate receptor molecules can then be employed to design ligands selective for receptor subtype through the novel methods of freeze-frame, click chemistry that uses the very structure of the target molecule as a template for synthesis of the inhibitor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.