ArticleThe Biochemical journal2005
PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 66 citations in OpenAlex.
- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
- Review
- A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.The EMBO journal · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis ineLife · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis inbioRxiv : the preprint server for biology · 2023Article
- AScience advances · 2023Article
- Exploring Potential Antimalarial Candidate from Medicinal Plants of Kheaw Hom Remedy.Tropical medicine and infectious disease · 2022Article
- Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites.mSphere · 2022Article
- Characterization of the cAMP phosphodiesterase domain in plant adenylyl cyclase/cAMP phosphodiesterase CAPE from the liverwort Marchantia polymorpha.Journal of plant research · 2022Article
- Article
- Plasticity and therapeutic potential of cAMP and cGMP-specific phosphodiesterases inComputational and structural biotechnology journal · 2022Article
- Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes.Nature communications · 2020Article
- The protozoan parasiteComputational and structural biotechnology journal · 2020Article
- An unusual and vital protein with guanylate cyclase and P4-ATPase domains in a pathogenic protist.Life science alliance · 2019Article
- Targeting malaria parasite invasion of red blood cells as an antimalarial strategy.FEMS microbiology reviews · 2019Review
- Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion.PLoS biology · 2019Article
- Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.International journal of molecular sciences · 2019Review
- Cyclic nucleotide signalling in malaria parasites.Open biology · 2017Review
- Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target.PLoS neglected tropical diseases · 2017Article
- Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage.Frontiers in immunology · 2017Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This is the first report of molecular characterization of a novel cyclic nucleotide PDE (phosphodiesterase), isolated from the human malaria parasite Plasmodium falciparum and designated PfPDE1. PfPDE1 cDNA encodes an 884-amino-acid protein, including six putative transmembrane domains in the N-terminus followed by a catalytic domain. The PfPDE1 gene is a single-copy gene consisting of two exons and a 170 bp intron. PfPDE1 transcripts were abundant in the ring form of the asexual blood stages of the parasite. The C-terminal catalytic domain of PfPDE1, produced in Escherichia coli, specifically hydrolysed cGMP with a K(m) value of 0.65 microM. Among the PDE inhibitors tested, a PDE5 inhibitor, zaprinast, was the most effective, having an IC50 value of 3.8 microM. The non-specific PDE inhibitors IBMX (3-isobutyl-1-methylxanthine), theophylline and the antimalarial chloroquine had IC50 values of over 100 microM. Membrane fractions prepared from P. falciparum at mixed asexual blood stages showed potent cGMP hydrolytic activity compared with cytosolic fractions. This hydrolytic activity was sensitive to zaprinast with an IC50 value of 4.1 microM, but insensitive to IBMX and theophylline. Furthermore, an in vitro antimalarial activity assay demonstrated that zaprinast inhibited the growth of the asexual blood parasites, with an ED50 value of 35 microM. The impact of cyclic nucleotide signalling on the cellular development of this parasite has previously been discussed. Thus this enzyme is suggested to be a novel potential target for the treatment of the disease malaria.
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