ArticleNature structural & molecular biology2018
Orthosteric and allosteric action of the C5a receptor antagonists.
Article in Nature structural & molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Atypical signaling, ligand recognition and selective agonist discovery of complement receptor C5aR2.Cell research · 2026Article
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- Complement C5a/C5aR1 pathway facilitates glioblastoma progression via fostering glioma stem cell-macrophage symbiosis.Journal of neuroinflammation · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Article
- Structural analysis reveals that water molecules mediate self-activation of GPR99.Communications biology · 2026Article
- The pathway-independent positive allosteric modulator C1 allows for the identification of active YCellular and molecular life sciences : CMLS · 2026Article
- Biased Allosteric Modulation in GPCR Drug Discovery.Handbook of experimental pharmacology · 2026Review
- Molecular insights into ago-allosteric modulation at cysteinyl leukotriene receptor 2.Nature communications · 2025Article
- A novel long-acting C5a-blocking cyclic peptide prevents sepsis-induced organ dysfunction via effective blockade of the inflammatory cascade.Signal transduction and targeted therapy · 2025Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Effects of chemosynthetic choline plasmalogens on gonadotropin secretion from bovine gonadotrophs.The Journal of reproduction and development · 2025Article
- Cryo-EM reveals an extrahelical allosteric binding site at the MNature communications · 2025Article
- Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.Developmental neuroscience · 2025Article
- Structural basis for full-length chemerin recognition and signaling through chemerin receptor 1.Communications biology · 2024Article
- Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential.Journal of chemical information and modeling · 2024Article
- Exploration of compounds to inhibit the Panton-Valentine leukocidin of Staphylococcus aureus.Medical microbiology and immunology · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The C5a receptor (C5aR) is a G-protein-coupled receptor (GPCR) that can induce strong inflammatory response to the anaphylatoxin C5a. Targeting C5aR has emerged as a novel anti-inflammatory therapeutic method. However, developing potent C5aR antagonists as drugs has proven difficult. Here, we report two crystal structures of human C5aR in ternary complexes with the peptide antagonist PMX53 and a non-peptide antagonist, either avacopan or NDT9513727. The structures, together with other biophysical, computational docking and cell-based signaling data, reveal the orthosteric action of PMX53 and its effect of stabilizing the C5aR structure, as well as the allosteric action of chemically diverse non-peptide C5aR antagonists with different binding poses. Structural comparison analysis suggests the presence of similar allosteric sites in other GPCRs. We also discuss critical structural features of C5aR in activation, including a novel conformation of helix 8. On the basis of our results, we suggest novel strategies for developing C5aR-targeting drugs.
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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.