ArticleThe Journal of biological chemistry2013
Ligand binding to anion-binding exosites regulates conformational properties of thrombin.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 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
- Engineering Linker-Enhanced OmpG Nanopores for Rapid Single-Molecule Protease Detection.Sensors (Basel, Switzerland) · 2025Article
- Investigating Protein-Nucleic Acid Binding Interactions with Diethylpyrocarbonate Covalent Labeling-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Proteins Can Withstand More Extensive Labeling while Providing Accurate Structural Information in Covalent Labeling-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- Thrombomodulin is essential for maintaining quiescence in vascular endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments.Frontiers in immunology · 2021Article
- Role of the protease-activated receptor 1 in regulating the function of glial cells within central and peripheral nervous system.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- Thrombin Exosite Maturation and Ligand Binding at ABE II Help Stabilize PAR-Binding Competent Conformation at ABE I.Biochemistry · 2019Article
- Comparison of Effects of Anti-thrombin Aptamers HD1 and HD22 on Aggregation of Human Platelets, Thrombin Generation, Fibrin Formation, and Thrombus Formation Under Flow Conditions.Frontiers in pharmacology · 2019Article
- Allosteric inhibition of α-thrombin enzymatic activity with ultrasmall gold nanoparticles.Nanoscale advances · 2019Article
- Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding site of thrombin.Thrombosis research · 2018Article
- Deciphering Conformational Changes Associated with the Maturation of Thrombin Anion Binding Exosite I.Biochemistry · 2017Article
- Targeting PAR1: Now What?Trends in pharmacological sciences · 2017Review
- Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers.Nucleic acids research · 2017Article
- NMR reveals a dynamic allosteric pathway in thrombin.Scientific reports · 2017Article
- Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.Scientific reports · 2016Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Thrombin participates in coagulation, anticoagulation, and initiation of platelet activation. To fulfill its diverse roles and maintain hemostasis, this serine protease is regulated via the extended active site region and anion-binding exosites (ABEs) I and II. For the current project, amide proton hydrogen-deuterium exchange coupled with MALDI-TOF mass spectrometry was used to characterize ligand binding to individual exosites and to investigate the presence of exosite-active site and exosite-exosite interactions. PAR3(44-56) and PAR1(49-62) were observed to bind to thrombin ABE I and then to exhibit long range effects over to ABE II. By contrast, Hirudin(54-65) focused more on ABE I and did not transmit influences over to ABE II. Although these three ligands were each directed to ABE I, they did not promote the same conformational consequences. D-Phe-Pro-Arg-chloromethyl ketone inhibition at the thrombin active site led to further local and long range consequences to thrombin-ABE I ligand complexes with the autolysis loop often most affected. When Hirudin(54-65) was bound to ABE I, it was still possible to bind GpIbα(269-286) or fibrinogen γ'(410-427) to ABE II. Each ligand exerted its predominant influences on thrombin and also allowed interexosite communication. The results obtained support the proposal that thrombin is a highly dynamic protein. The transmission of ligand-specific local and long range conformational events is proposed to help regulate this multifunctional enzyme.
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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.