ArticleThe Journal of biological chemistry2010
A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Microbiota-derived indole differentially shapes Entamoeba histolytica physiology and promotes host-compatible colonization.PLoS neglected tropical diseases · 2026Article
- Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens-Factors Linked to Virulence and Pathogenicity.International journal of molecular sciences · 2023Review
- Review
- Entamoeba histolytica exploits the autophagy pathway in macrophages to trigger inflammation in disease pathogenesis.Mucosal immunology · 2021Article
- Entamoeba histolytica activation of caspase-1 degrades cullin that attenuates NF-κB dependent signaling from macrophages.PLoS pathogens · 2021Article
- The Dichloromethane Fraction ofFrontiers in cellular and infection microbiology · 2021Article
- Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis.Frontiers in cellular and infection microbiology · 2020Review
- Entamoeba histolytica Interaction with Enteropathogenic Escherichia coli Increases Parasite Virulence and Inflammation in Amebiasis.Infection and immunity · 2019Article
- Review
- Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action.Microbiology and molecular biology reviews : MMBR · 2018Review
- Identification of cysteine protease inhibitors as new drug leads against Naegleria fowleri.Experimental parasitology · 2018Article
- Soluble expression of an amebic cysteine protease in the cytoplasm of Escherichia coli SHuffle Express cells and purification of active enzyme.BMC biotechnology · 2018Article
- Article
- The macrophage cytoskeleton acts as a contact sensor upon interaction with Entamoeba histolytica to trigger IL-1β secretion.PLoS pathogens · 2017Article
- Entamoeba histolytica Cysteine Proteinase 5 Evokes Mucin Exocytosis from Colonic Goblet Cells via αvβ3 Integrin.PLoS pathogens · 2016Article
- Putrescine-dependent re-localization of TvCP39, a cysteine proteinase involved in Trichomonas vaginalis cytotoxicity.PloS one · 2014Article
- Entamoeba histolytica: gene expression analysis of cells invading tissues.TheScientificWorldJournal · 2014Article
- Article
- Proteases from Entamoeba spp. and Pathogenic Free-Living Amoebae as Virulence Factors.Journal of tropical medicine · 2013Article
- Transcriptome analysis of encystation in Entamoeba invadens.PloS one · 2013Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 4 countries.
Funding
Abstract
Entamoeba histolytica cysteine proteinases (EhCPs) play a key role in disrupting the colonic epithelial barrier and the innate host immune response during invasion of E. histolytica, the protozoan cause of human amebiasis. EhCPs are encoded by 50 genes, of which ehcp4 (ehcp-a4) is the most up-regulated during invasion and colonization in a mouse cecal model of amebiasis. Up-regulation of ehcp4 in vivo correlated with our finding that co-culture of E. histolytica trophozoites with mucin-producing T84 cells increased ehcp4 expression up to 6-fold. We have expressed recombinant EhCP4, which was autocatalytically activated at acidic pH but had highest proteolytic activity at neutral pH. In contrast to the other amebic cysteine proteinases characterized so far, which have a preference for arginine in the P2 position, EhCP4 displayed a unique preference for valine and isoleucine at P2. This preference was confirmed by homology modeling, which revealed a shallow, hydrophobic S2 pocket. Endogenous EhCP4 localized to cytoplasmic vesicles, the nuclear region, and perinuclear endoplasmic reticulum (ER). Following co-culture with colonic cells, EhCP4 appeared in acidic vesicles and was released extracellularly. A specific vinyl sulfone inhibitor, WRR605, synthesized based on the substrate specificity of EhCP4, inhibited the recombinant enzyme in vitro and significantly reduced parasite burden and inflammation in the mouse cecal model. The unique expression pattern, localization, and biochemical properties of EhCP4 could be exploited as a potential target for drug design.
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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.