ArticleJournal of computer-aided molecular design2011
Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor.
Article in Journal of computer-aided molecular design, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 35 citations in OpenAlex.
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- Mapping the Binding Sites of UDP and Prostaglandin E2 Glyceryl Ester in the Nucleotide Receptor P2YChemMedChem · 2022Article
- Membrane Environment Modulates Ligand-Binding Propensity of P2Y12 Receptor.Pharmaceutics · 2021Article
- Two highly related odorant receptors specifically detect α-bile acid pheromones in sea lamprey (The Journal of biological chemistry · 2020Article
- Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.Frontiers in pharmacology · 2020Review
- Prostaglandin EScientific reports · 2017Article
- Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information.Journal of computer-aided molecular design · 2015Article
- Molecular modeling of the human P2Y14 receptor: A template for structure-based design of selective agonist ligands.Bioorganic & medicinal chemistry · 2015Article
- Article
- Further studies on 2-arylacetamide pyridazin-3(2H)-ones: design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists.European journal of medicinal chemistry · 2013Article
- 4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2YMedChemComm · 2013Article
- Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates.Journal of medicinal chemistry · 2013Review
- Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12.Molecular pharmacology · 2013Article
- Probing GPCR structure: adenosine and P2Y nucleotide receptors.Methods in enzymology · 2013Article
- Molecular Structure of P2Y Receptors: Mutagenesis, Modeling, and Chemical Probes.Wiley interdisciplinary reviews. Membrane transport and signaling · 2012Article
- G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions.Purinergic signalling · 2012Review
- Farnesyl pyrophosphate is an endogenous antagonist to ADP-stimulated P2Y₁₂ receptor-mediated platelet aggregation.Thrombosis and haemostasis · 2012Article
- Molecular docking of 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derived small-molecule agonists of human formyl peptide receptor 1.Journal of molecular modeling · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The P2Y(12) receptor (P2Y(12)R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs. Three homology models of P2Y(12)R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A(2A) adenosine receptor (A(2A)AR), and human C-X-C chemokine receptor type 4 (CXCR4). By criteria of sequence analysis (25.6% identity in transmembrane region), deviation from helicity in the second transmembrane helix (TM2), docked poses of ligands highlighting the role of key residues, accessibility of a conserved disulfide bridge that is reactive toward irreversibly-binding antagonists, and the presence of a shared disulfide bridge between the third extracellular loop (EL3) and the N-terminus, the CXCR4-based model appeared to be the most consistent with known characteristics of P2Y(12)R. The docked poses of agonist 2MeSADP and charged anthraquinone antagonist PSB-0739 in the binding pocket of P2Y(12)R-CXC agree with previously published site-directed mutagenesis studies of Arg256 and Lys280. A sulfonate at position 2 of the anthraquinone core created a strong interaction with the Lys174(EL2) side chain. The docking poses of the irreversibly-binding, active metabolite (existing as two diastereoisomers in vivo) of the clinically utilized antagonist Clopidogrel were compared. The free thiol group of the 4S diastereoisomer, but not the 4R isomer, was found in close proximity (~4.7 Å) to the sulfur atom of a disulfide bridge involving Cys175, suggesting greater activity in covalent binding. Therefore, ligand docking to the CXCR4-based model of the P2Y(12)R predicted poses of both reversibly and irreversibly-binding small molecules, consistent with observed pharmacology and mutagenesis studies.
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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 Socratic graph.