ArticleBlood2019
NMR structure determination of Ixolaris and factor X(a) interaction reveals a noncanonical mechanism of Kunitz inhibition.
Article in Blood, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- A novel polypeptide from stony coral Goniopora columna inhibits thrombosis by interfering with the contact-kinin pathway.Archives of toxicology · 2025Article
- Article
- Functional characterization of a common XIa inhibitory Kunitz-domain Shp4 from nine schistosoma secreted proteins with diverse C-terminal fragments.PLoS neglected tropical diseases · 2025Article
- Article
- Toward non-factor therapy in hemophilia: an antithrombin insensitive Gla-domainless factor Xa as tissue factor pathway inhibitor bait.Research and practice in thrombosis and haemostasis · 2023Article
- A Deeper Insight into the Tick Salivary Protein Families under the Light of Alphafold2 and Dali: Introducing the TickSialoFam 2.0 Database.International journal of molecular sciences · 2022Article
- A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate.Frontiers in molecular biosciences · 2022Review
- Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite-Host Crosstalk.International journal of molecular sciences · 2021Review
- Development ofClinical & experimental metastasis · 2020Article
- Cysteines and Disulfide Bonds as Structure-Forming Units: Insights From Different Domains of Life and the Potential for Characterization by NMR.Frontiers in chemistry · 2020Review
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6 authors at 3 institutions in 2 countries.
Funding
Abstract
Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, with formation of a quaternary tissue factor (TF)/FVIIa/ FX(a)/Ixolaris inhibitory complex. Ixolaris blocks TF-induced coagulation and PAR2 signaling and prevents thrombosis, tumor growth, and immune activation. We present a high-resolution structure and dynamics of Ixolaris and describe the structural basis for recognition of FX. Ixolaris consists of 2 Kunitz domains (K1 and K2) in which K2 is strikingly dynamic and encompasses several residues involved in FX binding. This indicates that the backbone plasticity of K2 is critical for Ixolaris biological activity. Notably, a nuclear magnetic resonance-derived model reveals a mechanism for an electrostatically guided, high-affinity interaction between Ixolaris and FX heparin-binding (pro)exosite, resulting in an allosteric switch in the catalytic site. This is the first report revealing the structure-function relationship of an anticoagulant targeting a zymogen serving as a scaffold for TF inhibition.
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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.