ReviewJournal of thrombosis and haemostasis : JTH2021
Proteolytic activity of contact factor zymogens.
Review in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Prekallikrein: the catalytic crossroads of inflammation and thrombosis.Current opinion in hematology · 2026Review
- Lipopolysaccharide and Coagulation Factor XII: Biophysics of Contact Activation in Infection.Seminars in thrombosis and hemostasis · 2026Review
- Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies.Biomolecules · 2026Review
- Bacterial infection and activation of the contact pathway of coagulation.Blood vessels, thrombosis & hemostasis · 2025Review
- Contact activation of coagulation in newly inserted indwelling catheters.Scientific reports · 2025Observational
- The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.The Journal of biological chemistry · 2025Article
- Artificial Zymogen Based on Protein-Polymer Hybrids.Biomacromolecules · 2024Article
- A mechanistic model of in vitro plasma activation to evaluate therapeutic kallikrein-kinin system inhibitors.PLoS computational biology · 2024Article
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood.Blood advances · 2024Article
- A Novel Trypsin Kunitz-Type Inhibitor from Cajanus cajan Leaves and Its Inhibitory Activity on New Cancer Serine Proteases and Its Effect on Tumor Cell Growth.The protein journal · 2024Article
- The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.Biomolecules · 2023Review
- Circulating prekallikrein levels are correlated with lipid levels in the chinese population: a cross-sectional study.Lipids in health and disease · 2023Article
- Combined oral contraceptives may activate the contact system in healthy women.Research and practice in thrombosis and haemostasis · 2023Article
- Oral FXIIa inhibitor KV998086 suppresses FXIIa and single chain FXII mediated kallikrein kinin system activation.Frontiers in pharmacology · 2023Article
- Cryo-EM structures of coagulation factors.Research and practice in thrombosis and haemostasis · 2022Review
- Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.Blood advances · 2022Article
- Novel Plasma Kallikrein Inhibitors for Treating Hereditary Angioedema, Diabetic Macular Edema, and Diabetic Retinopathy.ACS medicinal chemistry letters · 2022Article
- Coagulation and complement: Key innate defense participants in a seamless web.Frontiers in immunology · 2022Review
- Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Contact activation is triggered when blood is exposed to compounds or "surfaces" that promote conversion of the plasma zymogens factor XII (FXII) and prekallikrein to the active proteases FXIIa and kallikrein. FXIIa promotes blood coagulation by converting zymogen factor XI (FXI) to the protease FXIa. Contact activation appears to represent an enhancement of the propensity for FXII and prekallikrein to reciprocally activate each other by surface-independent limited proteolysis. The nature of the activities that perpetuate this process, and that trigger contact activation, are debated. FXII and prekallikrein, like most members of the chymotrypsin/trypsin protease family, are synthesized as single polypeptides that are presumed to be in an inactive state. Internal cleavage leads to conformational changes in the protease domain that convert the enzyme active site from a closed conformation to an open conformation accessible to substrates. We observed that FXII expresses a low level of activity as a single-chain zymogen that catalyzes prekallikrein activation in solution, as well as surface-dependent activation of prekallikrein, FXI, and FXII (autoactivation). Prekallikrein also expresses activity that promotes cleavage of kininogen to release bradykinin, and surface-dependent FXII activation. Modeling suggests that a glutamine residue at position 156 in the FXII and prekallikrein protease domains stabilizes an open active site conformation by forming hydrogen bonds with Asp194. The activity inherent in FXII and prekallikrein suggests a mechanism for sustaining reciprocal activation of the proteins and for initiating contact activation, and supports the premise that zymogens of some trypsin-like enzymes are active proteases.
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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.