ArticleThe Journal of biological chemistry2002
Identification by site-directed mutagenesis of residues involved in ligand recognition and activation of the human A3 adenosine receptor.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
56 citing papers in PubMed, 137 citations in OpenAlex.
- Molecular basis of ligand binding and receptor activation at the human ANature communications · 2025Article
- Pyrazolo-triazolo-pyrimidine Scaffold as a Molecular Passepartout for the Pan-Recognition of Human Adenosine Receptors.Biomolecules · 2023Article
- Species dependence of APurinergic signalling · 2023Review
- Pharmacological characterisation of novel adenosine AScientific reports · 2020Article
- In Silico Drug Design for Purinergic GPCRs: Overview on Molecular Dynamics Applied to Adenosine and P2Y Receptors.Biomolecules · 2020Review
- Truncated (N)-Methanocarba Nucleosides as Partial Agonists at Mouse and Human AJournal of medicinal chemistry · 2020Article
- Binding site matching in rational drug design: algorithms and applications.Briefings in bioinformatics · 2019Review
- AJournal of computer-aided molecular design · 2019Article
- Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy.Molecules (Basel, Switzerland) · 2019Article
- Free-Energy Calculations for Bioisosteric Modifications of AInternational journal of molecular sciences · 2019Article
- A non-functional galanin receptor-2 in a multiple sclerosis patient.The pharmacogenomics journal · 2019Article
- AMedicinal research reviews · 2018Review
- Studies on enantioselectivity of chiral 4-acetylamino-6-alkyloxy-2-alkylthiopyrimidines acting as antagonists of the human AMedChemComm · 2018Article
- The Polymorphism inBioMed research international · 2018Article
- Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.Molecules (Basel, Switzerland) · 2017Review
- Conserved Residues Control Activation of Mammalian G Protein-Coupled Odorant Receptors.Journal of the American Chemical Society · 2015Article
- Sodium ion binding pocket mutations and adenosine A2A receptor function.Molecular pharmacology · 2015Article
- Article
- Generic GPCR residue numbers - aligning topology maps while minding the gaps.Trends in pharmacological sciences · 2015Review
- Effect of a toggle switch mutation in TM6 of the human adenosine A₃ receptor on Gi protein-dependent signalling and Gi-independent receptor internalization.British journal of pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Ligand recognition has been extensively explored in G protein-coupled A(1), A(2A), and A(2B) adenosine receptors but not in the A(3) receptor, which is cerebroprotective and cardioprotective. We mutated several residues of the human A(3) adenosine receptor within transmembrane domains 3 and 6 and the second extracellular loop, which have been predicted by previous molecular modeling to be involved in the ligand recognition, including His(95), Trp(243), Leu(244), Ser(247), Asn(250), and Lys(152). The N250A mutant receptor lost the ability to bind both radiolabeled agonist and antagonist. The H95A mutation significantly reduced affinity of both agonists and antagonists. In contrast, the K152A (EL2), W243A (6.48), and W243F (6.48) mutations did not significantly affect the agonist binding but decreased antagonist affinity by approximately 3-38-fold, suggesting that these residues were critical for the high affinity of A(3) adenosine receptor antagonists. Activation of phospholipase C by wild type (WT) and mutant receptors was measured. The A(3) agonist 2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine stimulated phosphoinositide turnover in the WT but failed to evoke a response in cells expressing W243A and W243F mutant receptors, in which agonist binding was less sensitive to guanosine 5'-gamma-thiotriphosphate than in WT. Thus, although not important for agonist binding, Trp(243) was critical for receptor activation. The results were interpreted using a rhodopsin-based model of ligand-A(3) receptor interactions.
Indexed as
Identifiers
What OpenQuestion holds
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.