ArticleBiochemistry2008
A hydrogen bond in loop A is critical for the binding and function of the 5-HT3 receptor.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HTResearch (Washington, D.C.) · 2025Article
- Mapping the molecular motions of 5-HTeLife · 2024Article
- Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- A triad of residues is functionally transferrable between 5-HTThe Journal of biological chemistry · 2018Article
- The binding orientations of structurally-related ligands can differ; A cautionary note.Neuropharmacology · 2017Article
- Varenicline Interactions at the 5-HT3 Receptor Ligand Binding Site are Revealed by 5-HTBP.ACS chemical neuroscience · 2015Article
- Allosteric activation of the 5-HT3AB receptor by mCPBG.Neuropharmacology · 2015Article
- Article
- Unraveling mechanisms underlying partial agonism in 5-HT3A receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors.Neuropharmacology · 2014Article
- In vivo incorporation of non-canonical amino acids by using the chemical aminoacylation strategy: a broadly applicable mechanistic tool.Chembiochem : a European journal of chemical biology · 2014Review
- Functional probes of drug-receptor interactions implicated by structural studies: Cys-loop receptors provide a fertile testing ground.Journal of medicinal chemistry · 2014Review
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- Approaching the 5-HT₃ receptor heterogeneity by computational studies of the transmembrane and intracellular domains.Journal of computer-aided molecular design · 2013Article
- Structure-activity relationships of quinoxaline-based 5-HT3A and 5-HT3AB receptor-selective ligands.ChemMedChem · 2013Article
- Structural basis of ligand recognition in 5-HT3 receptors.EMBO reports · 2013Article
- 5-HT(3) receptors.The Journal of biological chemistry · 2012Review
- Design, synthesis, and structure-activity relationships of highly potent 5-HT₃ receptor ligands.Journal of medicinal chemistry · 2012Article
- A coupled array of noncovalent interactions impacts the function of the 5-HT3A serotonin receptor in an agonist-specific way.ACS chemical neuroscience · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The binding sites of Cys-loop receptors are formed from at least six loops (A-F). Here we have used mutagenesis, radioligand binding, voltage clamp electrophysiology, and homology modeling to probe the role of two residues in loop A of the 5-HT3 receptor: Asn128 and Glu129. The data show that substitution of Asn128, with a range of alternative natural and unnatural amino acids, changed the EC50 (from approximately 10-fold more potent to approximately 10-fold less potent than that of the wild type), increased the maximal peak current for mCPBG compared to 5-HT (R max) 2-19-fold, and decreased n H, indicating this residue is involved in receptor gating; we propose Asn128 faces away from the binding pocket and plays a role in facilitating transitions between conformational states. Substitutions of Glu129 resulted in functional receptors only when the residue could accept a hydrogen bond, but with both these and other substitutions, no [(3)H]granisetron binding could be detected, indicating a role in ligand binding. We propose that Glu129 faces into the binding pocket, where, through its ability to hydrogen bond, it plays a critical role in ligand binding. Thus, the data support a modified model of the 5-HT3 receptor binding site and show that loop A plays a critical role in both the ligand binding and function of this receptor.
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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.