ArticleThe Journal of biological chemistry2011
Allosteric model of maraviroc binding to CC chemokine receptor 5 (CCR5).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- HIV-1 subtype C predicted co-receptor tropism in Africa: an individual sequence level meta-analysis.AIDS research and therapy · 2020Pooled it
- Trial
- HIV gp120 induces TREM1 expression through TLR-PGE₂ signalling in human monocyte-derived microglia.Journal of neuroinflammation · 2026Article
- Combining AlphaFold with Focused Virtual Library Design in the Development of Novel CCR2 and CCR5 Antagonists.Journal of chemical information and modeling · 2025Article
- Targeting of specific CCR5-G protein complexes underlies biased signaling by HIV-1 envelope glycoproteins.Cell communication and signaling : CCS · 2025Article
- Identification and interaction mechanism of novel small molecule antagonists targeting CC chemokine receptor 1/3/5 for treatment of non-small cell lung cancer.Molecular diversity · 2025Article
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- CCR5 promotes the migration of pathological CD8+ T cells to the leishmanial lesions.PLoS pathogens · 2024Article
- JAK/STAT signaling pathway affects CCR5 expression in human CD4Science advances · 2024Article
- The chemokine receptor CCR5: multi-faceted hook for HIV-1.Retrovirology · 2024Review
- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- CCR5 promotes the migration of CD8bioRxiv : the preprint server for biology · 2023Article
- Pan-cancer functional analysis of somatic mutations in G protein-coupled receptors.Scientific reports · 2022Article
- Triazolyl Ru(II), Os(II), and Ir(III) complexes as potential HIV-1 inhibitors.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Article
- HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages.PLoS pathogens · 2022Article
- Evolution of CCR5 and CCR2 Genes in Bats Showed Multiple Independent Gene Conversion Events.Viruses · 2022Article
- CCR5 as a Coreceptor for Human Immunodeficiency Virus and Simian Immunodeficiency Viruses: A Prototypic Love-Hate Affair.Frontiers in immunology · 2022Review
- Modeling of CCR5 Recognition by HIV-1 gp120: How the Viral Protein Exploits the Conformational Plasticity of the Coreceptor.Viruses · 2021Article
- Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity.Journal of medicinal chemistry · 2021Article
- Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.Virulence · 2020Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maraviroc is a nonpeptidic small molecule human immunodeficiency virus type 1 (HIV-1) entry inhibitor that has just entered the therapeutic arsenal for the treatment of patients. We recently demonstrated that maraviroc binding to the HIV-1 coreceptor, CC chemokine receptor 5 (CCR5), prevents it from binding the chemokine CCL3 and the viral envelope glycoprotein gp120 by an allosteric mechanism. However, incomplete knowledge of ligand-binding sites and the lack of CCR5 crystal structures have hampered an in-depth molecular understanding of how the inhibitor works. Here, we addressed these issues by combining site-directed mutagenesis (SDM) with homology modeling and docking. Six crystal structures of G-protein-coupled receptors were compared for their suitability for CCR5 modeling. All CCR5 models had equally good geometry, but that built from the recently reported dimeric structure of the other HIV-1 coreceptor CXCR4 bound to the peptide CVX15 (Protein Data Bank code 3OE0) best agreed with the SDM data and discriminated CCR5 from non-CCR5 binders in a virtual screening approach. SDM and automated docking predicted that maraviroc inserts deeply in CCR5 transmembrane cavity where it can occupy three different binding sites, whereas CCL3 and gp120 lie on distinct yet overlapped regions of the CCR5 extracellular loop 2. Data suggesting that the transmembrane cavity remains accessible for maraviroc in CCL3-bound and gp120-bound CCR5 help explain our previous observation that the inhibitor enhances dissociation of preformed ligand-CCR5 complexes. Finally, we identified residues in the predicted CCR5 dimer interface that are mandatory for gp120 binding, suggesting that receptor dimerization might represent a target for new CCR5 entry inhibitors.
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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.