ReviewThe Journal of general physiology2018
Toward an understanding of the structural basis of allostery in muscarinic acetylcholine receptors.
Review in The Journal of general physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Structural Perspectives on Biased Allostery of GPCR Signaling.Handbook of experimental pharmacology · 2026Review
- The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.British journal of pharmacology · 2025Review
- Cryo-EM reveals an extrahelical allosteric binding site at the MNature communications · 2025Article
- A New Era of Muscarinic Acetylcholine Receptor Modulators in Neurological Diseases, Cancer and Drug Abuse.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- Positive allosteric modulation of a GPCR ternary complex.Science advances · 2024Article
- Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor.The Journal of biological chemistry · 2024Article
- Guided diffusion for molecular generation with interaction prompt.Briefings in bioinformatics · 2024Article
- Extrahelical Binding Site for a 1Molecular pharmacology · 2024Article
- The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.British journal of pharmacology · 2023Article
- Xanomeline displays concomitant orthosteric and allosteric binding modes at the MNature communications · 2023Article
- Recessive CHRM5 variant as a potential cause of neurogenic bladder.American journal of medical genetics. Part A · 2023Article
- Differential Activity of Orthosteric Agonists and Allosteric Modulators at Metabotropic Glutamate Receptor 7.Molecular pharmacology · 2023Article
- Article
- Conservation of Allosteric Ligand Binding Sites in G-Protein Coupled Receptors.Journal of chemical information and modeling · 2022Article
- Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery.Trends in pharmacological sciences · 2021Review
- Repositioning Dequalinium as Potent Muscarinic Allosteric Ligand by Combining Virtual Screening Campaigns and Experimental Binding Assays.International journal of molecular sciences · 2020Article
- Computational insights into the molecular mechanisms of differentiated allosteric modulation at the mu opioid receptor by structurally similar bitopic modulators.Journal of computer-aided molecular design · 2020Article
- Article
- Current Advances in Allosteric Modulation of Muscarinic Receptors.Biomolecules · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent breakthroughs and developments in structural biology have led to a spate of crystal structures for G protein-coupled receptors (GPCRs). This is the case for the muscarinic acetylcholine receptors (mAChRs) where inactive-state structures for four of the five subtypes and two active-state structures for one subtype are available. These mAChR crystal structures have provided new insights into receptor mechanisms, dynamics, and allosteric modulation. This is highly relevant to the mAChRs given that these receptors are an exemplar model system for the study of GPCR allostery. Allosteric mechanisms of the mAChRs are predominantly consistent with a two-state model, albeit with some notable recent exceptions. Herein, we discuss the mechanisms for positive and negative allosteric modulation at the mAChRs and compare and contrast these to evidence offered by pharmacological, biochemical, and computational approaches. This analysis provides insight into the fundamental pharmacological properties exhibited by GPCR allosteric modulators, such as enhanced subtype selectivity, probe dependence, and biased modulation while highlighting the current challenges that remain. Though complex, enhanced molecular understanding of allosteric mechanisms will have considerable influence on our understanding of GPCR activation and signaling and development of therapeutic interventions.
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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.