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Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors

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    SYSNO ASEP0360455
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors
    Author(s) Horn, Martin (UOCHB-X) RID, ORCID
    Jílková, Adéla (UOCHB-X) RID, ORCID
    Vondrášek, Jiří (UOCHB-X) RID, ORCID
    Marešová, Lucie (UOCHB-X) RID
    Caffrey, C. R. (US)
    Mareš, Michael (UOCHB-X) RID, ORCID
    Number of authors6
    Source TitleACS Chemical Biology. - : American Chemical Society - ISSN 1554-8929
    Roč. 6, č. 6 (2011), s. 609-617
    Number of pages9 s.
    Languageeng - English
    CountryUS - United States
    KeywordsSchistosoma mansoni ; cathepsin B ; propeptide
    Subject RIVCE - Biochemistry
    R&D ProjectsGA203/09/1585 GA ČR - Czech Science Foundation (CSF)
    KJB400550516 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
    IAA400550705 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
    CEZAV0Z40550506 - UOCHB-X (2005-2011)
    UT WOS000291896400011
    DOI10.1021/cb100411v
    AnnotationBlood flukes of the genus Schistosoma cause the disease schistosomiasis that infects over 200 million people worldwide. Schistosoma mansoni cathepsin B1 (SmCB1) is a gut-associated protease that digests host blood proteins as source of nutrients. Enzymatic activity of the SmCB1 zymogen is prevented by the pro-peptide that sterically blocks the active site until activation of the zymogen to the mature enzyme. We investigated the structure-inhibition relationships of how the SmCB1 pro-peptide interacts with the enzyme core using a SmCB1 zymogen model and pro-peptide-derived synthetic fragments. Two regions were identified within the pro-peptide that govern its inhibitory interaction with the enzyme core: an 'active site region' and a unique 'heparin-binding region' that requires heparin. Using the active site region as a template and a docking model of SmCB1, we designed a series of inhibitors mimicking the pro-peptide structure.
    WorkplaceInstitute of Organic Chemistry and Biochemistry
    Contactasep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
    Year of Publishing2012
Number of the records: 1  

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