ArticleNature structural & molecular biology2017
Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 64 citations in OpenAlex.
- Structure-guided design of a PCSK9 epitope vaccine with efficacy against hyperlipidemia and atherosclerosis.Life metabolism · 2026Article
- PCSK9 as a Potential Regulator of Endothelial Dysfunction: Mechanistic Insights and Future Directions.International journal of molecular sciences · 2026Review
- A Machine Learning-Enabled Venom Peptide Platform for Rapid Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Enhanced sensitivity in PCSK9 detection using binding-induced DNA walker-triggered Argonaute protein-based DNA circuit.Mikrochimica acta · 2025Article
- Cholesterol reduction by immunization with a PCSK9 mimic.Cell reports · 2024Article
- Therapeutic peptides for coronary artery diseases: in silico methods and current perspectives.Amino acids · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Disulfide-constrained peptide scaffolds enable a robust peptide-therapeutic discovery platform.PloS one · 2024Article
- Inhibition of PCSK9: A Promising Enhancer for Anti-PD-1/PD-L1 Immunotherapy.Research (Washington, D.C.) · 2024Review
- Functional Characterization of p.(Arg160Gln) PCSK9 Variant Accidentally Found in a Hypercholesterolemic Subject.International journal of molecular sciences · 2023Article
- Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration.Nature communications · 2022Article
- Charge-Sensitive Optical Detection of Binding Kinetics between Phage-Displayed Peptide Ligands and Protein Targets.Biosensors · 2022Article
- Current Evidence and Future Directions of PCSK9 Inhibition.US cardiology · 2021Review
- Regulation of Lipoprotein Homeostasis by Self-Assembling Peptides.ACS applied bio materials · 2020Article
- From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators.European journal of medicinal chemistry · 2020Article
- The novel llama-human chimeric antibody has potent effect in lowering LDL-c levels in hPCSK9 transgenic rats.Clinical and translational medicine · 2020Article
- Proprotein convertase subtilisin/kexin type 9 and lipid metabolism.Current opinion in lipidology · 2019Review
- Inhibition of PCSK9ACS medicinal chemistry letters · 2019Article
- Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies.Cardiovascular research · 2019Review
- Biological Characterization of Computationally Designed Analogs of peptide TVFTSWEEYLDWV (Pep2-8) with Increased PCSK9 Antagonistic Activity.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma LDL cholesterol (LDL-c) levels by promoting the degradation of liver LDL receptors (LDLRs). Antibodies that inhibit PCSK9 binding to the EGF(A) domain of the LDLR are effective in lowering LDL-c. However, the discovery of small-molecule therapeutics is hampered by difficulty in targeting the relatively flat EGF(A)-binding site on PCSK9. Here we demonstrate that it is possible to target this site, based on the finding that the PCSK9 P' helix displays conformational flexibility. As a consequence, the vacated N-terminal groove of PCSK9, which is adjacent to the EGF(A)-binding site, is in fact accessible to small peptides. In phage-display experiments, the EGF(A)-mimicking peptide Pep2-8 was used as an anchor peptide for the attachment of an extension peptide library directed toward the groove site. Guided by structural information, we further engineered the identified groove-binding peptides into antagonists, which encroach on the EGF(A)-binding site and inhibit LDLR binding.
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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.