ArticleThe Journal of biological chemistry2013
Characterization of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) and its role in microneme secretion during erythrocyte invasion.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 94 citations in OpenAlex.
- Physiology of invasiveFrontiers in cellular and infection microbiology · 2026Review
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- Gene expression analyses reveal differences in children's response to malaria according to their age.bioRxiv : the preprint server for biology · 2023Article
- A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.Communications biology · 2023Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
- Decrypting the complexity of the human malaria parasite biology through systems biology approaches.Frontiers in systems biology · 2022Article
- Intracellular CaInternational journal of molecular sciences · 2021Review
- CDPKs: The critical decoders of calcium signal at various stages of malaria parasite development.Computational and structural biotechnology journal · 2021Review
- Calcium in the Backstage of Malaria Parasite Biology.Frontiers in cellular and infection microbiology · 2021Review
- cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition ofFrontiers in microbiology · 2021Review
- An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- In vitro effects of 5 recombinant antigens of Eimeria maxima on maturation, differentiation, and immunogenic functions of dendritic cells derived from chicken spleen.Poultry science · 2020Article
- Article
- Whole-Cell Phenotypic Screening of Medicines for Malaria Venture Pathogen Box Identifies Specific Inhibitors ofAntimicrobial agents and chemotherapy · 2020Article
- Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs.Memorias do Instituto Oswaldo Cruz · 2020Review
- The Novel Serine/Threonine Protein Kinase LmjF.22.0810 fromBiomolecules · 2019Article
- Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019Review
- Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.PLoS biology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium-dependent protein kinases (CDPKs) play important roles in the life cycle of Plasmodium falciparum and other apicomplexan parasites. CDPKs commonly have an N-terminal kinase domain (KD) and a C-terminal calmodulin-like domain (CamLD) with calcium-binding EF hands. The KD and CamLD are separated by a junction domain (JD). Previous studies on Plasmodium and Toxoplasma CDPKs suggest a role for the JD and CamLD in the regulation of kinase activity. Here, we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)). Moreover, site-directed mutagenesis of conserved hydrophobic residues in the JD (F363A/I364A, L356A, and F350A) abrogates functional activity of PfCDPK1, demonstrating the importance of these residues in PfCDPK1 function. Modeling studies suggest that these residues play a role in interaction of the CamLD with the JD. The P3 peptide, which specifically inhibits the functional activity of PfCDPK1, blocks microneme discharge and erythrocyte invasion by P. falciparum merozoites. Purfalcamine, a previously identified specific inhibitor of PfCDPK1, also inhibits microneme discharge and erythrocyte invasion, confirming a role for PfCDPK1 in this process. These studies validate PfCDPK1 as a target for drug development and demonstrate that interfering with its mechanistic regulation may provide a novel approach to design-specific PfCDPK1 inhibitors that limit blood stage parasite growth and clear malaria parasite infections.
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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.