ArticleBMC biochemistry2002
Functional group interactions of a 5-HT3R antagonist.
Article in BMC biochemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- The binding orientations of structurally-related ligands can differ; A cautionary note.Neuropharmacology · 2017Article
- The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors.Neuropharmacology · 2014Article
- Structure-activity relationships of quinoxaline-based 5-HT3A and 5-HT3AB receptor-selective ligands.ChemMedChem · 2013Article
- 5-HT(3) receptors.The Journal of biological chemistry · 2012Review
- Molecular actions of smoking cessation drugs at α4β2 nicotinic receptors defined in crystal structures of a homologous binding protein.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Bivalent Ligands for the Serotonin 5-HT3 Receptor.ACS medicinal chemistry letters · 2011Article
- The 5-HT3 receptor--the relationship between structure and function.Neuropharmacology · 2009Review
- The 5-HT3 receptor as a therapeutic target.Expert opinion on therapeutic targets · 2007Review
- Subunit rotation models activation of serotonin 5-HT3AB receptors by agonists.Journal of computer-aided molecular design · 2004Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLerisetron, a competitive serotonin type 3 receptor (5-HT3R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT3R binding site. Site directed mutagenesis studies of the 5-HT3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site.
resultsTwo analogs of lerisetron were synthesized to probe 5-HT3R functional group interactions with this compound. Analog 1 lacks the N1 benzyl group of lerisetron and analog 2 contains oxygen in place of the distal piperazine nitrogen. Both analogs show significantly decreased binding affinity to wildtype 5-HT3ASRs. Mutations at W89, R91, Y142 and Y152 produced significant decreases in binding compared to wildtype receptors. Binding affinities of analogs 1 and 2 were altered only by mutations at W89, and Y152.
conclusionsBased on the data obtained for lerisetron and analogs 1 and 2, we have proposed a tentative model of the lerisetron binding pocket of the 5-HT3ASR. According to this model, The N-benzyl group interacts in a weak interaction with R91 while the benzimidazole group interacts with W89. Our data support an interaction of the distal amino nitrogen with Y142 and Y152.
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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.