ArticleProceedings of the National Academy of Sciences of the United States of America2002
The cAMP-specific phosphodiesterase TbPDE2C is an essential enzyme in bloodstream form Trypanosoma brucei.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. 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, 70 citations in OpenAlex.
- Exploring the Activity Profile of TbrPDEB1 and hPDE4 Inhibitors Using Free Energy Perturbation.ACS medicinal chemistry letters · 2022Article
- Cloning and functional complementation of ten Schistosoma mansoni phosphodiesterases expressed in the mammalian host stages.PLoS neglected tropical diseases · 2020Article
- Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity.Journal of medicinal chemistry · 2018Article
- Article
- The ever unfolding story of cAMP signaling in trypanosomatids: vive la difference!Frontiers in pharmacology · 2015Review
- Cyclic AMP effectors in African trypanosomes revealed by genome-scale RNA interference library screening for resistance to the phosphodiesterase inhibitor CpdA.Antimicrobial agents and chemotherapy · 2013Article
- Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure.Journal of medicinal chemistry · 2013Article
- Pharmacological validation of Trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness.Journal of medicinal chemistry · 2011Article
- Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite.Future medicinal chemistry · 2011Article
- Target repurposing for neglected diseases.Future medicinal chemistry · 2011Article
- The N terminus of phosphodiesterase TbrPDEB1 of Trypanosoma brucei contains the signal for integration into the flagellar skeleton.Eukaryotic cell · 2010Article
- The Trypanosoma brucei flagellum: moving parasites in new directions.Annual review of microbiology · 2009Review
- Silencing of six hydrophobins in Cladosporium fulvum: complexities of simultaneously targeting multiple genes.Applied and environmental microbiology · 2009Article
- Gene silencing by RNA Interference in the white rot fungus Phanerochaete chrysosporium.Applied and environmental microbiology · 2008Article
- The flagellum of Trypanosoma brucei: new tricks from an old dog.International journal for parasitology · 2008Review
- Testing the efficacy of RNA interference constructs in Aspergillus fumigatus.Current genetics · 2007Article
- Hydrolysis products of cAMP analogs cause transformation of Trypanosoma brucei from slender to stumpy-like forms.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Characterization of a novel cAMP-binding, cAMP-specific cyclic nucleotide phosphodiesterase (TcrPDEB1) from Trypanosoma cruzi.The Biochemical journal · 2006Article
- Cyclic nucleotide specific phosphodiesterases of Leishmania major.BMC microbiology · 2006Article
- PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum.The Biochemical journal · 2005Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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Abstract
Chemotherapy of human sleeping sickness, a fatal disease caused by the protozoan parasite Trypanosoma brucei, is in a dismal state, and the identification and characterization of new drug targets is an urgent prerequisite for an improvement of the dramatic situation in the field. Over the last several years, inhibitors of cyclic nucleotide-specific phosphodiesterases have proven to be highly successful drug candidates for an assortment of clinical conditions. Their potential as antiparasitic drugs has not been explored so far. This study reports the characterization of a cAMP-specific phosphodiesterase from T. brucei, TbPDE2C. This enzyme is a class I phosphodiesterase, and it is a member of a small enzyme family in T. brucei, TbPDE2. Inhibitors of this enzyme block the proliferation of bloodstream form trypanosomes in culture. RNA interference experiments demonstrated that the TbPDE2 family, and in particular TbPDE2C, are essential for maintaining intracellular cAMP concentrations within a physiological range. Bloodstream form trypanosomes are exquisitely sensitive to elevated concentrations of intracellular cAMP, and a disruption of TbPDE2C function quickly leads to the disruption of nuclear and cellular cell division, and to cell death. TbPDE2C might represent a novel drug target for the development of new and effective trypanocidal drugs.
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