ArticleThe Journal of biological chemistry2011
Crystal structure of plasminogen activator inhibitor-1 in an active conformation with normal thermodynamic stability.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition.The Journal of biological chemistry · 2022Article
- A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?International journal of molecular sciences · 2021Review
- Dissecting molecular details and functional effects of the high-affinity copper binding site in plasminogen activator Inhibitor-1.Protein science : a publication of the Protein Society · 2021Article
- Plasminogen activator inhibitor-1: a potential etiological role in livedoid vasculopathy.International wound journal · 2020Review
- 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
- Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition.Frontiers in cardiovascular medicine · 2020Review
- Characterization of an Extensive Interface on Vitronectin for Binding to Plasminogen Activator Inhibitor-1: Adoption of Structure in an Intrinsically Disordered Region.Biochemistry · 2019Article
- Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1.Scientific reports · 2019Article
- Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice: Implications for Adhesions Therapy.Scientific reports · 2018Article
- Resolving distinct molecular origins for copper effects on PAI-1.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
- Conformational preludes to the latency transition in PAI-1 as determined by atomistic computer simulations and hydrogen/deuterium-exchange mass spectrometry.Scientific reports · 2017Article
- Single fluorescence probes along the reactive center loop reveal site-specific changes during the latency transition of PAI-1.Protein science : a publication of the Protein Society · 2016Article
- Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop.Protein science : a publication of the Protein Society · 2016Article
- Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain.Frontiers in microbiology · 2015Article
- Characterization of a small molecule inhibitor of plasminogen activator inhibitor type 1 that accelerates the transition into the latent conformation.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serpin plasminogen activator inhibitor-1 (PAI-1) is a crucial regulator in fibrinolysis and tissue remodeling. PAI-1 has been associated with several pathological conditions and is a validated prognostic marker in human cancers. However, structural information about the native inhibitory form of PAI-1 has been elusive because of its inherent conformational instability and rapid conversion to a latent, inactive structure. Here we report the crystal structure of PAI-1 W175F at 2.3 Å resolution as the first model of the metastable native molecule. Structural comparison with a quadruple mutant (14-1B) previously used as representative of the active state uncovered key differences. The most striking differences occur near the region that houses three of the four mutations in the 14-1B PAI-1 structure. Prominent changes are localized within a loop connecting β-strand 3A with the F helix, in which a previously observed 3(10)-helix is absent in the new structure. Notably these structural changes are found near the binding site for the cofactor vitronectin. Because vitronectin is the only known physiological regulator of PAI-1 that slows down the latency conversion, the structure of this region is important. Furthermore, the previously identified chloride-binding site close to the F-helix is absent from the present structure and likely to be artifactual, because of its dependence on the 14-1B mutations. Instead we found a different chlorine-binding site that is likely to be present in wild type PAI-1 and that more satisfactorily accounts for the chlorine stabilizing effect on PAI-1.
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