ArticleBiochemistry2013
Remarkable stabilization of plasminogen activator inhibitor 1 in a "molecular sandwich" complex.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- Plasminogen Activator Inhibitor 1 for Predicting Sepsis Severity and Mortality Outcomes: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2018Pooled it
- Meta-Analysis of Preclinical Studies of Fibrinolytic Therapy for Acute Lung Injury.Frontiers in immunology · 2018Pooled it
- INHIBITING THE INHIBITOR: WOULD TARGETING PAI-1 RESULT IN A LOW-DOSE, WELL-TOLERATED TREATMENT OF EMPYEMA?Biomedical sciences instrumentation · 2025Article
- Precision targeting of the plasminogen activator inhibitor-1 mechanism increases efficacy of fibrinolytic therapy in empyema.Physiological reports · 2021Article
- 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
- Targeting plasminogen activator inhibitor-1 in tetracycline-induced pleural injury in rabbits.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase.Journal of cellular and molecular medicine · 2016Article
- The High Affinity Binding Site on Plasminogen Activator Inhibitor-1 (PAI-1) for the Low Density Lipoprotein Receptor-related Protein (LRP1) Is Composed of Four Basic Residues.The Journal of biological chemistry · 2016Article
- Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits.American journal of respiratory cell and molecular biology · 2015Article
- Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release.Frontiers in microbiology · 2015Article
- Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs.Intrinsically disordered proteins · 2014Article
- Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner.Journal of hematology & oncology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Plasminogen activator inhibitor 1 (PAI-1) levels are elevated in a number of life-threatening conditions and often correlate with unfavorable outcomes. Spontaneous inactivation due to active to latent transition limits PAI-1 activity in vivo. While endogenous vitronectin (Vn) stabilizes PAI-1 by 1.5-2.0-fold, further stabilization occurs in a "molecular sandwich" complex (MSC) in which a ligand that restricts the exposed reactive center loop is bound to PAI-1/Vn. The effects of S195A two-chain urokinase (tcuPA) and Vn on inactivation of wild-type (wt) glycosylated (Gl-PAI-1), nonglycosylated (rPAI-1), and nonglycosylated Q123K PAI-1 (lacks Vn binding) forms were studied. S195A tcuPA decreased the rate constant (kL) for spontaneous inactivation at 37 °C for rPAI-1, Q123K, and Gl-PAI-1 by 6.7-, 3.4-, and 7.8-fold, respectively, and both S195A tcuPA and Vn by 66.7-, 5.5-, and 103.3-fold, respectively. Analysis of the temperature dependences of kL revealed a synergistic increase in the Gibbs free activation energy for spontaneous inactivation of wt Gl-PAI-1 and rPAI-1 in MSC from 99.8 and 96.1 to 111.3 and 107.0 kJ/mol, respectively, due to an increase in the activation enthalpy and a decrease in the activation entropy. Anti-PAI-1 monoclonal antibodies (mAbs) competing with proteinase also stabilize PAI-1/Vn. The rate of inhibition of target proteinases by MSCs, with a stoichiometry close to unity, was limited by the dissociation (k = 10(-4) to 10(-3) s(-1)) of S195A tcuPA or mAb. The stabilization of PAI-1 in MSCs in vivo may potentiate uncontrolled thrombosis or extravascular fibrin deposition, suggesting a new paradigm for using PAI-1 inhibitors and novel potential targets for therapy.
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