ArticleScientific reports2021
The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular modeling design of antitrypanosomal pyrazolone derivatives targeting Chagas disease: QSAR, docking, molecular dynamics and free energy calculations.Journal of molecular modeling · 2026Article
- Chagas disease: host responses, parasite evasion and vaccine advances.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2026Review
- To Explore Potential Natural Inhibitors of Cysteine Proteases to Combat Human African Trypanosomiasis and Chagas Disease.Current medicinal chemistry · 2026Review
- Unraveling Common Patterns and Differences among Cruzipains through Molecular Dynamics Simulations and Structural Analyses.ACS omega · 2025Article
- Thiosulfonate-Based Targeted Covalent Cruzipain Inhibitors with Enhanced Bioactivity Translation for Antichagasic Therapy.ACS medicinal chemistry letters · 2025Article
- Discovery of a Potent Triazole-Based Reversible Targeted Covalent Inhibitor of Cruzipain.ACS medicinal chemistry letters · 2025Article
- Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease.Memorias do Instituto Oswaldo Cruz · 2025Article
- Insights into the Antiparasitic Activity of Pyrazole-benzimidazole againstCurrent medicinal chemistry · 2025Article
- Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.Molecules (Basel, Switzerland) · 2024Article
- Comparative membrane proteomic analysis of Tritrichomonas foetus isolates.Scientific reports · 2024Article
- Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.Current medicinal chemistry · 2024Review
- Article
- Screening the Pathogen Box to Discover and Characterize New Cruzain andPathogens (Basel, Switzerland) · 2023Article
- From rational design to serendipity: Discovery of novel thiosemicarbazones as potent trypanocidal compounds.European journal of medicinal chemistry · 2022Article
- Review
- Computational approaches towards the discovery and optimisation of cruzain inhibitors.Memorias do Instituto Oswaldo Cruz · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.
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