ArticleAngewandte Chemie (International ed. in English)2016
The Molecular Mechanism of P2Y1 Receptor Activation.
Article in Angewandte Chemie (International ed. in English), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Synthesis, preclinical evaluation and pilot clinical study of a P2YActa pharmaceutica Sinica. B · 2025Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- The P2YBMC gastroenterology · 2024Article
- A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular disease.American journal of blood research · 2023Review
- The full activation mechanism of the adenosine AProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mapping the Binding Sites of UDP and Prostaglandin E2 Glyceryl Ester in the Nucleotide Receptor P2YChemMedChem · 2022Article
- Interaction With the Lipid Membrane Influences Fentanyl Pharmacology.Advances in drug and alcohol research · 2022Article
- Neuroprotective Roles of the Adenosine ANeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Update of P2Y receptor pharmacology: IUPHAR Review 27.British journal of pharmacology · 2020Review
- In Silico Drug Design for Purinergic GPCRs: Overview on Molecular Dynamics Applied to Adenosine and P2Y Receptors.Biomolecules · 2020Review
- Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18.Biomolecules · 2020Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compounds.Communications biology · 2019Article
- Exploring a new ligand binding site of G protein-coupled receptors.Chemical science · 2018Article
- Demystifying P2YJournal of chemical information and modeling · 2017Article
- Conformation and dynamics of the C-terminal region in human phosphoglycerate mutase 1.Acta pharmacologica Sinica · 2017Article
- Designing Safer Analgesics via μ-Opioid Receptor Pathways.Trends in pharmacological sciences · 2017Review
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 5 institutions in 4 countries.
Funding
Abstract
Human purinergic G protein-coupled receptor P2Y1 (P2Y1 R) is activated by adenosine 5'-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y1 R revealed that one ligand (MRS2500) binds to the extracellular vestibule of this GPCR, whereas another (BPTU) occupies the surface between transmembrane (TM) helices TM2 and TM3. We introduced a total of 20 μs all-atom long-timescale molecular dynamic (MD) simulations to inquire why two molecules in completely different locations both serve as antagonists while ADP activates the receptor. Our results indicate that BPTU acts as an antagonist by stabilizing extracellular helix bundles leading to an increase of the lipid order, whereas MRS2500 blocks signaling by occupying the ligand binding site. Both antagonists stabilize an ionic lock within the receptor. However, binding of ADP breaks this ionic lock, forming a continuous water channel that leads to P2Y1 R activation.
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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.