ArticleThe Journal of biological chemistry2011
Structural basis for inhibition of cathepsin B drug target from the human blood fluke, Schistosoma mansoni.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 82 citations in OpenAlex.
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- Catalytically Active Recombinant Cysteine Proteases ofInternational journal of molecular sciences · 2025Article
- A genome-scale drug discovery pipeline uncovers new therapeutic targets and a unique p97 allosteric binding site inbioRxiv : the preprint server for biology · 2025Article
- Computational Workflow to Design Novel Vaccine Candidates and Small-Molecule Therapeutics for Schistosomiasis.Pathogens (Basel, Switzerland) · 2024Article
- Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhibition of the Cathepsin B1 Protease Target and Binding Mode Analysis.ACS infectious diseases · 2024Article
- Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity.ACS omega · 2024Article
- An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans.International journal of molecular sciences · 2024Article
- Targeting SmCB1: Perspectives and Insights to Design Antischistosomal Drugs.Current medicinal chemistry · 2024Review
- Drug Discovery Efforts to Identify Novel Treatments for Neglected Tropical Diseases - Cysteine Protease Inhibitors.Current medicinal chemistry · 2024Review
- Transcriptomic and proteomic profiling of peptidase expression in Fasciola hepatica eggs developing at host's body temperature.Scientific reports · 2022Article
- De Novo Design of Cathepsin B1 Inhibitors as Potential Anti-Schistosomal Agents Using Computational Studies.Advances and applications in bioinformatics and chemistry : AABC · 2022Article
- The Zoonotic Helminth ParasiteAnimals : an open access journal from MDPI · 2021Article
- Article
- A comprehensive and critical overview of schistosomiasis vaccine candidates.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2021Review
- 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
- Differential expression profiles of miRNAs and their putative targets in Schistosoma mansoni during its life cycle.Memorias do Instituto Oswaldo Cruz · 2021Article
- Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.Frontiers in immunology · 2021Review
- Serine proteases activity in miracidia ofVeterinary research forum : an international quarterly journal · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schistosomiasis caused by a parasitic blood fluke of the genus Schistosoma afflicts over 200 million people worldwide. Schistosoma mansoni cathepsin B1 (SmCB1) is a gut-associated peptidase that digests host blood proteins as a source of nutrients. It is under investigation as a drug target. To further this goal, we report three crystal structures of SmCB1 complexed with peptidomimetic inhibitors as follows: the epoxide CA074 at 1.3 Å resolution and the vinyl sulfones K11017 and K11777 at 1.8 and 2.5 Å resolutions, respectively. Interactions of the inhibitors with the subsites of the active-site cleft were evaluated by quantum chemical calculations. These data and inhibition profiling with a panel of vinyl sulfone derivatives identify key binding interactions and provide insight into the specificity of SmCB1 inhibition. Furthermore, hydrolysis profiling of SmCB1 using synthetic peptides and the natural substrate hemoglobin revealed that carboxydipeptidase activity predominates over endopeptidolysis, thereby demonstrating the contribution of the occluding loop that restricts access to the active-site cleft. Critically, the severity of phenotypes induced in the parasite by vinyl sulfone inhibitors correlated with enzyme inhibition, providing support that SmCB1 is a valuable drug target. The present structure and inhibitor interaction data provide a footing for the rational design of anti-schistosomal inhibitors.
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