ArticleThe Journal of biological chemistry2009
Long range communication between exosites 1 and 2 modulates thrombin function.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 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
30 citing papers in PubMed, 75 citations in OpenAlex.
- 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
- From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).Protein science : a publication of the Protein Society · 2023Article
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- Article
- Platelet glycoprotein V spatio-temporally controls fibrin formation.Nature cardiovascular research · 2023Article
- Current Status of Oligonucleotide-Based Protein Degraders.Pharmaceutics · 2023Review
- Mathematical modeling to understand the role of bivalent thrombin-fibrin binding during polymerization.PLoS computational biology · 2022Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- Spectroscopic Properties of Two 5'-(4-Dimethylamino)Azobenzene Conjugated G-Quadruplex Forming Oligonucleotides.International journal of molecular sciences · 2020Article
- γ' fibrinogen levels are associated with blood clot strength in traumatic brain injury patients.American journal of surgery · 2020Article
- A Mathematical Model of Bivalent Binding Suggests Physical Trapping of Thrombin within Fibrin Fibers.Biophysical journal · 2019Article
- Thrombin Exosite Maturation and Ligand Binding at ABE II Help Stabilize PAR-Binding Competent Conformation at ABE I.Biochemistry · 2019Article
- Identification and characterization of a factor Va-binding site on human prothrombin fragment 2.Scientific reports · 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
- Molecular dynamics simulations of aptamer-binding reveal generalized allostery in thrombin.Journal of biomolecular structure & dynamics · 2017Article
- Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers.Nucleic acids research · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although exosites 1 and 2 regulate thrombin activity by binding substrates and cofactors and by allosterically modulating the active site, it is unclear whether there is direct allosteric linkage between the two exosites. To begin to address this, we first titrated a thrombin variant fluorescently labeled at exosite 1 with exosite 2 ligands, HD22 (a DNA aptamer), gamma'-peptide (an analog of the COOH terminus of the gamma'-chain of fibrinogen) or heparin. Concentration-dependent and saturable changes in fluorescence were elicited, supporting inter-exosite linkage. To explore the functional consequences of this phenomenon, we evaluated the capacity of exosite 2 ligands to inhibit thrombin binding to gamma(A)/gamma(A)-fibrin, an interaction mediated solely by exosite 1. When gamma(A)/gamma(A)-fibrinogen was clotted with thrombin in the presence of HD22, gamma'-peptide, or prothrombin fragment 2 there was a dose-dependent and saturable decrease in thrombin binding to the resultant fibrin clots. Furthermore, HD22 reduced the affinity of thrombin for gamma(A)/gamma(A)-fibrin 6-fold and accelerated the dissociation of thrombin from preformed gamma(A)/gamma(A)-fibrin clots. Similar responses were obtained when surface plasmon resonance was used to monitor the interaction of thrombin with gamma(A)/gamma(A)-fibrinogen or fibrin. There is bidirectional communication between the exosites, because exosite 1 ligands, HD1 (a DNA aptamer) or hirudin-(54-65) (an analog of the COOH terminus of hirudin), inhibited the exosite 2-mediated interaction of thrombin with immobilized gamma'-peptide. These findings provide evidence for long range allosteric linkage between exosites 1 and 2 on thrombin, revealing further complexity to the mechanisms of thrombin regulation.
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.