ArticleThe Journal of biological chemistry2015
Crystal Structure of the Michaelis Complex between Tissue-type Plasminogen Activator and Plasminogen Activators Inhibitor-1.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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, 52 citations in OpenAlex.
- Glucagon-like peptide-1 receptor agonist in large vessel occlusion treated by reperfusion therapy-a phase 2 randomized trial.Nature communications · 2025Trial
- SERPINE1/PAI-1 in Skeletal Degeneration: A Proposed Context-Dependent Framework for Bone Remodeling Regulation.Calcified tissue international · 2026Review
- A Contemporary Review of Plasminogen Activator Inhibitor Type 1: Structure, Function, Genetic Architecture, and Intracellular/Extracellular Roles.TH open : companion journal to thrombosis and haemostasis · 2025Review
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Fibrinolysis: an illustrated review.Research and practice in thrombosis and haemostasis · 2023Review
- Insights Into The Effects of Amino Acid Substitutions on The Stability of Reteplase Structure: A Molecular Dynamics Simulation Study.Iranian journal of biotechnology · 2023Article
- Transgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission.Nature communications · 2022Article
- Beyond cuts and scrapes: plasmin in malaria and other vector-borne diseases.Trends in parasitology · 2022Review
- Management of tandem occlusions in patients who receive rtPA.Journal of thrombosis and thrombolysis · 2021Article
- Structural Basis of Covalent Inhibitory Mechanism of TMPRSS2-Related Serine Proteases by Camostat.Journal of virology · 2021Article
- Structural Insight into the Two-Step Mechanism of PAI-1 Inhibition by Small Molecule TM5484.International journal of molecular sciences · 2021Article
- Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.International journal of molecular sciences · 2020Article
- Molecular mechanism of two nanobodies that inhibit PAI-1 activity reveals a modulation at distinct stages of the PAI-1/plasminogen activator interaction.Journal of thrombosis and haemostasis : JTH · 2020Article
- Therapeutics targeting the fibrinolytic system.Experimental & molecular medicine · 2020Review
- Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion.Nature communications · 2020Article
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- Enhancement of Expression Level of Modified t-PA (TNKase) in Leishmania tarentolae by Induction SystemIranian biomedical journal · 2019Article
- Biochemical and structural analyses suggest that plasminogen activators coevolved with their cognate protein substrates and inhibitors.The Journal of biological chemistry · 2019Article
- Reactive centre loop dynamics and serpin specificity.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombosis is a leading cause of death worldwide. Recombinant tissue-type plasminogen activator (tPA) is the Food and Drug Administration-approved thrombolytic drug. tPA is rapidly inactivated by endogenous plasminogen activator inhibitor-1 (PAI-1). Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort. Precise details, with atomic resolution, of the molecular interactions between tPA and PAI-1 remain unknown despite previous extensive studies. Here, we report the crystal structure of the tPA·PAI-1 Michaelis complex, which shows significant differences from the structure of its urokinase-type plasminogen activator analogue, the uPA·PAI-1 Michaelis complex. The PAI-1 reactive center loop adopts a unique kinked conformation. The structure provides detailed interactions between tPA 37- and 60-loops with PAI-1. On the tPA side, the S2 and S1β pockets open up to accommodate PAI-1. This study provides structural basis to understand the specificity of PAI-1 and to design newer generation of thrombolytic agents with reduced PAI-1 inactivation.
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.