ArticleProceedings of the National Academy of Sciences of the United States of America2014
The linker connecting the two kringles plays a key role in prothrombin activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 47 citations in OpenAlex.
- In vivo targeting of open prothrombin with the monoclonal antibody POmAb results in anticoagulation without excessive bleeding.Journal of thrombosis and haemostasis : JTH · 2026Article
- Dynamic nature of Staphylococcus aureus type I signal peptidases.Biophysical journal · 2025Article
- The Prothrombin-Prothrombinase Interaction.Sub-cellular biochemistry · 2024Review
- Comparative sequence analysis of vitamin K-dependent coagulation factors.Journal of thrombosis and haemostasis : JTH · 2022Article
- Cryo-EM structures of coagulation factors.Research and practice in thrombosis and haemostasis · 2022Review
- Article
- Binding modes of prothrombin cleavage site sequences to the factor Xa catalytic triad: Insights from atomistic simulations.Computational and structural biotechnology journal · 2022Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- Article
- Zymogen and activated protein C have similar structural architecture.The Journal of biological chemistry · 2020Article
- Residues W215, E217 and E192 control the allosteric E*-E equilibrium of thrombin.Scientific reports · 2019Article
- Probing prothrombin structure by limited proteolysis.Scientific reports · 2019Article
- Enhancing the anticoagulant profile of meizothrombin.Biomolecular concepts · 2018Article
- Interplay between conformational selection and zymogen activation.Scientific reports · 2018Article
- Structure of prothrombin in the closed form reveals new details on the mechanism of activation.Scientific reports · 2018Article
- Non-canonical proteolytic activation of human prothrombin by subtilisin fromThe Journal of biological chemistry · 2017Article
- Induced Fit Is a Special Case of Conformational Selection.Biochemistry · 2017Article
- Dual effect of histone H4 on prothrombin activation.Journal of thrombosis and haemostasis : JTH · 2016Article
- Structural Architecture of Prothrombin in Solution Revealed by Single Molecule Spectroscopy.The Journal of biological chemistry · 2016Article
- Loop Electrostatics Asymmetry Modulates the Preexisting Conformational Equilibrium in Thrombin.Biochemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that is accelerated >3,000-fold by cofactor Va. This physiologically important effect is paradigmatic of analogous cofactor-dependent reactions in the coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3). Recent developments indicate that the linkers, and particularly Lnk2, confer on the zymogen significant flexibility in solution and enable prothrombin to sample alternative conformations. The role of this flexibility in the context of prothrombin activation was tested with several deletions. Removal of Lnk2 in almost its entirety (ProTΔ146-167) drastically reduces the enhancement of thrombin generation by cofactor Va from >3,000-fold to 60-fold because of a significant increase in the rate of activation in the absence of cofactor. Deletion of Lnk2 mimics the action of cofactor Va and offers insights into how prothrombin is activated at the molecular level. The crystal structure of ProTΔ146-167 reveals a contorted architecture where the domains are not vertically stacked, kringle-1 comes within 9 Å of the protease domain, and the Gla-domain primed for membrane binding comes in contact with kringle-2. These findings broaden our molecular understanding of a key reaction of the blood coagulation cascade where cofactor Va enhances activation of prothrombin by factor Xa by compressing Lnk2 and morphing prothrombin into a conformation similar to the structure of ProTΔ146-167.
Indexed as
Identifiers
What OpenQuestion holds
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.