ArticleNature communications2024
Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Metabolic Gating and the Evolution of Human Cognitive Plasticity: A Comparative Genomic Analysis.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84.Nature communications · 2026Article
- Article
- Therapeutic strategies for hypertension: exploring the role of microbiota-derived short-chain fatty acids in kidney physiology and development.Pediatric nephrology (Berlin, Germany) · 2026Review
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Structures of G-protein coupled receptor HCAR3 in complex with selective agonists reveal the basis for ligand recognition and selectivity.PLoS biology · 2025Article
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors.bioRxiv : the preprint server for biology · 2025Article
- Structures of G-protein coupled receptor HCAR1 in complex with Gi1 protein reveal the mechanistic basis for ligand recognition and agonist selectivity.PLoS biology · 2025Article
- Structural visualization of small molecule recognition by CXCR3 uncovers dual-agonism in the CXCR3-CXCR7 system.Nature communications · 2025Article
- Molecular basis of promiscuous chemokine binding and structural mimicry at the C-X-C chemokine receptor, CXCR2.Molecular cell · 2025Article
- Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.Journal of medicinal chemistry · 2025Article
- Orphan GPCRs in Neurodegenerative Disorders: Integrating Structural Biology and Drug Discovery Approaches.Current issues in molecular biology · 2024Review
- Hypertriglyceridemia Therapy: Past, Present and Future Perspectives.International journal of molecular sciences · 2024Review
- Article
- Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode.Nature communications · 2024Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting 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.