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SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties
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SYSNO ASEP 0491001 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties Author(s) Leontovyč, Adrian (UOCHB-X) ORCID
Ulrychová, Lenka (UOCHB-X) ORCID, RID
O'Donoghue, A.J. (US)
Vondrášek, Jiří (UOCHB-X) RID, ORCID
Marešová, Lucie (UOCHB-X) RID
Hubálek, Martin (UOCHB-X) RID, ORCID
Fajtová, Pavla (UOCHB-X) RID, ORCID
Chanová, M. (CZ)
Jiang, Z. (US)
Craik, C. S. (US)
Caffrey, C. R. (US)
Mareš, Michael (UOCHB-X) RID, ORCID
Dvořák, Jan (UOCHB-X) ORCID
Horn, Martin (UOCHB-X) RID, ORCIDArticle number e0006446 Source Title PLoS Neglected Tropical Diseases. - : Public Library of Science - ISSN 1935-2735
Roč. 12, č. 4 (2018)Number of pages 26 s. Language eng - English Country US - United States Keywords Echinococcus granulosus ; cathepsin B ; molecular characterization Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects LD15101 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LH15040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LO1302 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UOCHB-X - RVO:61388963 UT WOS 000433487700071 EID SCOPUS 85046346355 DOI 10.1371/journal.pntd.0006446 Annotation Background: Serine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat (TSR-1). These proteases are recognized as antigens during host infection and may prove useful as anthelminthic vaccines, however their molecular characteristics are under-studied. Here, we characterize the structural and proteolytic attributes of serine protease 2 (SmSP2) from Schistosoma mansoni, one of the major species responsible for the tropical infectious disease, schistosomiasis. Methodology/Principal findings: SmSP2 comprises three domains: a histidine stretch, TSR-1 and a serine protease domain. The cleavage specificity of recombinant SmSP2 was determined using positional scanning and multiplex combinatorial libraries and the determinants of specificity were identified with 3D homology models, demonstrating a trypsin-like endopeptidase mode of action. SmSP2 displayed restricted proteolysis on protein substrates. It activated tissue plasminogen activator and plasminogen as key components of the fibrinolytic system, and released the vasoregulatory peptide, kinin, from kininogen. SmSP2 was detected in the surface tegument, esophageal glands and reproductive organs of the adult parasite by immunofluorescence microscopy, and in the excretory/secretory products by immunoblotting. Conclusions/Significance: The data suggest that SmSP2 is secreted, functions at the host-parasite interface and contributes to the survival of the parasite by manipulating host vasodilatation and fibrinolysis. SmSP2 may be, therefore, a potential target for anti-schistosomal therapy. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2019 Electronic address http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006446
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