ArticleScientific reports2016
The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- The expanding role of protease therapeutics (2012-2026): from replacement therapies to immune system modulation and beyond.The Biochemical journal · 2026Review
- Inhibition of DNA cleavage and strand passage activities of Mycobacterium tuberculosis topoisomerase I.Nucleic acids research · 2025Article
- Structural insights into proprotein convertase activation facilitate the engineering of highly specific furin inhibitors.Nature communications · 2025Article
- Protease engineering: Approaches, tools, and emerging trends.Biotechnology advances · 2025Review
- Development and Prospects of Furin Inhibitors for Therapeutic Applications.International journal of molecular sciences · 2024Review
- SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works.International journal of molecular sciences · 2023Article
- Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition.Molecules (Basel, Switzerland) · 2023Article
- Article
- A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro.Structure (London, England : 1993) · 2021Article
- Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.Communications biology · 2021Article
- A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entrybioRxiv : the preprint server for biology · 2020Article
- An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction.Nature communications · 2020Article
- The proprotein convertase furin is a pro-oncogenic driver in KRAS and BRAF driven colorectal cancer.Oncogene · 2020Article
- Structural Basis for the Specific Neutralization of Stx2a with a Camelid Single Domain Antibody Fragment.Toxins · 2018Article
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- Review
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Authors and funding
7 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2.0 Å and 2.3 Å, respectively. Nb14 binds at a site distant to the substrate binding pocket to the P-domain of furin. Interestingly, no major conformational changes were observed upon complex formation, neither for the protease nor for the antibody. Inhibition of furin by Nb14 is instead explained by steric exclusion of specific substrate conformers, explaining why Nb14 inhibits the processing of bulky protein substrates but not of small peptide substrates. This mode of action was further supported by modelling studies with the ternary factor X-furin-antibody complex and a mutation that disrupted the interaction interface between furin and the antibody. The observed binding mode of Nb14 suggests a novel approach for the development of highly specific antibody-based proprotein convertase inhibitors.
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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.