ArticleProceedings of the National Academy of Sciences of the United States of America2012
Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 157 citations in OpenAlex.
- Measurement of Active Thrombin Bound to Circulating D-Dimers as a Sensitive Biomarker for Prothrombotic Conditions.Journal of clinical laboratory analysis · 2026Article
- DRUMBEAT temporally resolved interpretable machine learning model for characterizing state transitions in protein dynamics.Communications biology · 2026Article
- Network Dynamics as Fingerprints of Thermostability in an In Silico-Engineered DyP-Type Peroxidase.ACS catalysis · 2025Article
- Dynamic nature of Staphylococcus aureus type I signal peptidases.Biophysical journal · 2025Article
- Identifying Inhibitor-SARS-CoV2-3CLMolecules (Basel, Switzerland) · 2025Article
- BaNDyT: Bayesian Network modeling of molecular Dynamics Trajectories.bioRxiv : the preprint server for biology · 2024Article
- NetSci: A Library for High Performance Biomolecular Simulation Network Analysis Computation.Journal of chemical information and modeling · 2024Article
- MEF-AlloSite: an accurate and robust Multimodel Ensemble Feature selection for the Allosteric Site identification model.Journal of cheminformatics · 2024Article
- Article
- Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine.Biophysical journal · 2024Article
- Complementary Pocket and Network-Based Approach to Search for Spike Protein Allosteric Pocket Sites.ACS omega · 2023Article
- Connected Component Analysis of Dynamical Perturbation Contact Networks.The journal of physical chemistry. B · 2023Article
- Unraveling the Role of Hydrogen Bonds in Thrombin via Two Machine Learning Methods.Journal of chemical information and modeling · 2023Article
- Article
- Dynamic allostery in thrombin-a review.Frontiers in molecular biosciences · 2023Review
- Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.Journal of medicinal chemistry · 2022Article
- Article
- A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa.Scientific reports · 2022Article
- How Thrombomodulin Enables W215A/E217A Thrombin to Cleave Protein C but Not Fibrinogen.Biochemistry · 2022Article
- Binding Analysis Using Accelerated Molecular Dynamics Simulations and Future Perspectives.Advances and applications in bioinformatics and chemistry : AABC · 2022Review
33 more citing papers are in PubMed but not listed here.
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 2 institutions in 1 country.
Funding
Abstract
The serine protease α-thrombin is a dual-action protein that mediates the blood-clotting cascade. Thrombin alone is a procoagulant, cleaving fibrinogen to make the fibrin clot, but the thrombin-thrombomodulin (TM) complex initiates the anticoagulant pathway by cleaving protein C. A TM fragment consisting of only the fifth and sixth EGF-like domains (TM56) is sufficient to bind thrombin, but the presence of the fourth EGF-like domain (TM456) is critical to induce the anticoagulant activity of thrombin. Crystallography of the thrombin-TM456 complex revealed no significant structural changes in thrombin, suggesting that TM4 may only provide a scaffold for optimal alignment of protein C for its cleavage by thrombin. However, a variety of experimental data have suggested that the presence of TM4 may affect the dynamic properties of the active site loops. In the present work, we have used both conventional and accelerated molecular dynamics simulation to study the structural dynamic properties of thrombin, thrombin:TM56, and thrombin:TM456 across a broad range of time scales. Two distinct yet interrelated allosteric pathways are identified that mediate both the pro- and anticoagulant activities of thrombin. One allosteric pathway, which is present in both thrombin:TM56 and thrombin:TM456, directly links the TM5 domain to the thrombin active site. The other allosteric pathway, which is only present on slow time scales in the presence of the TM4 domain, involves an extended network of correlated motions linking the TM4 and TM5 domains and the active site loops of thrombin.
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.