ArticleThe Journal of biological chemistry2016
A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior.
Article in The Journal of biological chemistry, 2016. 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.
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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, 37 citations in OpenAlex.
- Article
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Convergent strategies for nanobody-mediated inhibition of an epoxide hydrolase.bioRxiv : the preprint server for biology · 2026Article
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Exploring Proteases as Alternative Molecular Targets to Tackle Inflammation in Cystic Fibrosis Respiratory Infections.International journal of molecular sciences · 2025Review
- Enzymatic, structural, and biophysical characterization of a single-domain antibody (VHH) selectively and tightly inhibiting neutrophil elastase and exhibiting favorable developability properties.Protein science : a publication of the Protein Society · 2024Article
- Substrate derived sequences act as subsite-blocking motifs in protease inhibitory antibodies.Protein science : a publication of the Protein Society · 2023Article
- Insights into Comparative Modeling of VInternational journal of molecular sciences · 2021Article
- An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants.Structure (London, England : 1993) · 2021Article
- Selection and Modelling of a New Single-Domain Intrabody Against TDP-43.Frontiers in molecular biosciences · 2021Article
- Bivalent antibody pliers inhibit β-tryptase by an allosteric mechanism dependent on the IgG hinge.Nature communications · 2020Article
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
- Protease Inhibition Mechanism of Camelid-like Synthetic Human Antibodies.Biochemistry · 2020Article
- Camelid-derived single-chain antibodies in hemostasis: Mechanistic, diagnostic, and therapeutic applications.Research and practice in thrombosis and haemostasis · 2020Review
- Allosteric modulation of the GTPase activity of a bacterial LRRK2 homolog by conformation-specific Nanobodies.The Biochemical journal · 2020Article
- Isolation and structural characterization of a ZnThe Journal of biological chemistry · 2020Article
- Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody.Scientific reports · 2019Article
- Homology Modeling-Based in Silico Affinity Maturation Improves the Affinity of a Nanobody.International journal of molecular sciences · 2019Article
- Reducing proteolytic liability of a MMP-14 inhibitory antibody by site-saturation mutagenesis.Protein science : a publication of the Protein Society · 2019Article
- Beyond antibody engineering: directed evolution of alternative binding scaffolds and enzymes using yeast surface display.Microbial cell factories · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A peptide segment that binds the active site of a serine protease in a substrate-like manner may behave like an inhibitor or a substrate. However, there is sparse information on which factors determine the behavior a particular peptide segment will exhibit. Here, we describe the first x-ray crystal structure of a nanobody in complex with a serine protease. The nanobody displays a new type of interaction between an antibody and a serine protease as it inserts its complementary determining region-H3 loop into the active site of the protease in a substrate-like manner. The unique binding mechanism causes the nanobody to behave as a strong inhibitor as well as a poor substrate. Intriguingly, its substrate behavior is incomplete, as 30-40% of the nanobody remained intact and inhibitory after prolonged incubation with the protease. Biochemical analysis reveals that an intra-loop interaction network within the complementary determining region-H3 of the nanobody balances its inhibitor versus substrate behavior. Collectively, our results unveil molecular factors, which may be a general mechanism to determine the substrate versus inhibitor behavior of other protease 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.