ArticlePloS one2016
Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Covalent inhibitors of human papillomavirus type 16 E6 protein restore p53 function and suppress growth of HPV-driven tumors in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer.Journal of molecular cell biology · 2025Review
- Virtual Screening, Molecular Docking and Molecular Dynamics Simulation of Bioactive Compounds from Various Indonesian Medicinal Plants as Potential Inhibitors of Human Papillomavirus Type 16 E6 Protein in Cervical Cancer Development.Tropical life sciences research · 2025Article
- Structure of the p53 degradation complex from HPV16.Nature communications · 2024Article
- Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.Current medicinal chemistry · 2024Review
- Article
- In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.Pharmaceuticals (Basel, Switzerland) · 2021Review
- PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6.Molecules (Basel, Switzerland) · 2021Review
- A high-content AlphaScreen™ identifies E6-specific small molecule inhibitors as potential therapeutics for HPVOncotarget · 2021Article
- Identification of potential binding pocket on viral oncoprotein HPV16 E6: a promising anti-cancer target for small molecule drug discovery.BMC molecular and cell biology · 2019Article
- Molecular modeling simulation studies reveal new potential inhibitors against HPV E6 protein.PloS one · 2019Article
- A quantitative LumiFluo assay to test inhibitory compounds blocking p53 degradation induced by human papillomavirus oncoprotein E6 in living cells.Scientific reports · 2018Article
- Review
- Understanding the Role of Intrinsic Disorder of Viral Proteins in the Oncogenicity of Different Types of HPV.International journal of molecular sciences · 2018Article
- Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The human papillomavirus (HPV) HPV E6 protein has emerged as a central oncoprotein in HPV-associated cancers in which sustained expression is required for tumor progression. A majority of the E6 protein interactions within the human proteome use an alpha-helix groove interface for binding. The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface. This enables formation of a trimeric complex with p53, resulting in destruction of this tumor suppressor. While recent x-ray crystal structures are useful, examples of small molecule probes that can modulate protein interactions at this interface are limited. To develop insights useful for potential structure-based design of ligands for HPV E6, a series of 2,6-disubstituted benzopyranones were prepared and tested as competitive antagonists of E6-E6AP helix-groove interactions. These small molecule probes were used in both binding and functional assays to evaluate recognition features of the E6 protein. Evidence for an ionic functional group interaction within the helix groove was implicated by the structure-activity among the highest affinity ligands. The molecular topographies of these protein-ligand interactions were evaluated by comparing the binding and activities of single amino acid E6 mutants with the results of molecular dynamic simulations. A group of arginine residues that form a rim-cap over the E6 helix groove offer compensatory roles in binding and recognition of the small molecule probes. The flexibility and impact on the overall helix-groove shape dictated by these residues offer new insights for structure-based targeting of HPV E6.
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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.