ArticleThe Journal of biological chemistry2016
Non-equivalence of Key Positively Charged Residues of the Free Fatty Acid 2 Receptor in the Recognition and Function of Agonist Versus Antagonist Ligands.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- Structural insights into lipid chain-length selectivity and allosteric regulation of FFA2.Nature communications · 2025Article
- Development of a yeast-based sensor platform for evaluation of ligands recognized by the human free fatty acid 2 receptor.FEMS yeast research · 2025Article
- Structural basis for the ligand recognition and signaling of free fatty acid receptors.Science advances · 2024Article
- Discovery of Potent Tetrazole Free Fatty Acid Receptor 2 Antagonists.Journal of medicinal chemistry · 2023Article
- The allosterically modulated FFAR2 is transactivated by signals generated by other neutrophil GPCRs.PloS one · 2023Article
- α-Synuclein expression in response to bacterial ligands and metabolites in gut enteroendocrine cells: anBrain communications · 2023Article
- Article
- Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators.International journal of molecular sciences · 2021Review
- Participation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer.Frontiers in physiology · 2021Review
- Free Fatty Acid Receptors 2 and 3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View.Biomedicines · 2020Review
- Neutrophil Signaling That Challenges Dogmata of G Protein-Coupled Receptor Regulated Functions.ACS pharmacology & translational science · 2020Review
- Metabolomics of primary cutaneous melanoma and matched adjacent extratumoral microenvironment.PloS one · 2020Article
- Chemogenetics defines receptor-mediated functions of short chain free fatty acids.Nature chemical biology · 2019Article
- On-target and off-target effects of novel orthosteric and allosteric activators of GPR84.Scientific reports · 2019Article
- Microbial metabolite sensor GPR43 controls severity of experimental GVHD.Nature communications · 2018Article
- G protein-coupled receptors not currently in the spotlight: free fatty acid receptor 2 and GPR35.British journal of pharmacology · 2018Review
- Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology.Comprehensive Physiology · 2018Review
- FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- A single extracellular amino acid in Free Fatty Acid Receptor 2 defines antagonist species selectivity and G protein selection bias.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Short chain fatty acids (SCFAs) are produced in the gut by bacterial fermentation of poorly digested carbohydrates. A key mediator of their actions is the G protein-coupled free fatty acid 2 (FFA2) receptor, and this has been suggested as a therapeutic target for the treatment of both metabolic and inflammatory diseases. However, a lack of understanding of the molecular determinants dictating how ligands bind to this receptor has hindered development. We have developed a novel radiolabeled FFA2 antagonist to probe ligand binding to FFA2, and in combination with mutagenesis and molecular modeling studies, we define how agonist and antagonist ligands interact with the receptor. Although both agonist and antagonist ligands contain negatively charged carboxylates that interact with two key positively charged arginine residues in transmembrane domains V and VII of FFA2, there are clear differences in how these interactions occur. Specifically, although agonists require interaction with both arginine residues to bind the receptor, antagonists require an interaction with only one of the two. Moreover, different chemical series of antagonist interact preferentially with different arginine residues. A homology model capable of rationalizing these observations was developed and provides a tool that will be invaluable for identifying improved FFA2 agonists and antagonists to further define function and therapeutic opportunities of this receptor.
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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.