ArticleScientific reports2017
Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Convergent strategies for nanobody-mediated inhibition of an epoxide hydrolase.bioRxiv : the preprint server for biology · 2026Article
- The Light Chain Allosterically Enhances the Protease Activity of Murine Urokinase-Type Plasminogen Activator.Biochemistry · 2024Article
- Structural study of the uPA-nafamostat complex reveals a covalent inhibitory mechanism of nafamostat.Biophysical journal · 2022Article
- Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration.Nature communications · 2022Article
- Antibody recognition of complement factor H reveals a flexible loop involved in atypical hemolytic uremic syndrome pathogenesis.The Journal of biological chemistry · 2022Article
- Article
- Structure-mechanics statistical learning uncovers mechanical relay in proteins.Chemical science · 2022Article
- Urokinase plasminogen activator as an anti-metastasis target: inhibitor design principles, recent amiloride derivatives, and issues with human/mouse species selectivity.Biophysical reviews · 2022Review
- A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo.Nature communications · 2022Article
- A comprehensive comparison between camelid nanobodies and single chain variable fragments.Biomarker research · 2021Review
- Hydrogen/Deuterium Exchange and Nuclear Magnetic Resonance Spectroscopy Reveal Dynamic Allostery on Multiple Time Scales in the Serine Protease Thrombin.Biochemistry · 2021Article
- Structural Basis of Covalent Inhibitory Mechanism of TMPRSS2-Related Serine Proteases by Camostat.Journal of virology · 2021Article
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
- Camelid-derived single-chain antibodies in hemostasis: Mechanistic, diagnostic, and therapeutic applications.Research and practice in thrombosis and haemostasis · 2020Review
- Structure and development of single domain antibodies as modules for therapeutics and diagnostics.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Review
- Structural Biology and Protein Engineering of Thrombolytics.Computational and structural biotechnology journal · 2019Review
- Hydrogen-deuterium exchange mass spectrometry reveals folding and allostery in protein-protein interactions.Methods (San Diego, Calif.) · 2018Review
- Dynamic Consequences of Mutation of Tryptophan 215 in Thrombin.Biochemistry · 2018Article
- Interplay between conformational selection and zymogen activation.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two β-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general.
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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.