ArticlePLoS neglected tropical diseases2015
Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Fat or flat? The impact of dipole moment vectors on non-covalent interactions between aromatic tags and macromolecules.Inorganic chemistry frontiers · 2026Article
- Cryo-EM led analysis of open and closed conformations of Chagas vaccine candidate TcPOP.Nature communications · 2025Article
- Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhibition of the Cathepsin B1 Protease Target and Binding Mode Analysis.ACS infectious diseases · 2024Article
- Uncovering the essential roles of glutamate carboxypeptidase 2 orthologs in Caenorhabditis elegans.Bioscience reports · 2024Article
- COVID-19 and Diarylamidines: The Parasitic Connection.International journal of molecular sciences · 2023Review
- A comparative 'omics' approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens.PLoS neglected tropical diseases · 2023Article
- Assessment of reference genes at six different developmental stages of Schistosoma mansoni for quantitative RT-PCR.Scientific reports · 2021Article
- Spatial expression pattern of serine proteases in the blood fluke Schistosoma mansoni determined by fluorescence RNA in situ hybridization.Parasites & vectors · 2021Article
- Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors.ACS infectious diseases · 2021Article
- Azanitrile Inhibitors of the SmCB1 Protease Target Are Lethal toACS infectious diseases · 2021Article
- Serine proteases activity in miracidia ofVeterinary research forum : an international quarterly journal · 2021Article
- Review
- Article
- Prolyl Oligopeptidase FromFrontiers in microbiology · 2020Article
- SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties.PLoS neglected tropical diseases · 2018Article
- The blood fluke Schistosoma mansoni cleaves the coagulation protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin.Parasites & vectors · 2018Article
- Vesicle-based secretion in schistosomes: Analysis of protein and microRNA (miRNA) content of exosome-like vesicles derived from Schistosoma mansoni.Scientific reports · 2018Article
- Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses.Frontiers in immunology · 2018Review
- Article
- TRP channels in schistosomes.International journal for parasitology. Drugs and drug resistance · 2016Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBlood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. METHODOLOGY/PRINCIPAL
findingsWe demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. CONCLUSIONS/SIGNIFICANCE: We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs.
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