ArticleBMC genomics2022
Comparative analysis of the kinomes of Plasmodium falciparum, Plasmodium vivax and their host Homo sapiens.
Article in BMC genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Phosphorylation in theJournal of proteome research · 2024Pooled it
- FIKK1, a member of the FIKK kinase family, phosphorylates VAR2CSA and regulates adhesion of Plasmodium falciparum-infected erythrocytes to the placental receptor CSA.PLoS pathogens · 2026Article
- Curation of the Fasciola hepatica kinome as a resource for drug target discovery.BMC genomics · 2026Article
- Article
- Optimization of 2,8-Diaryl-1,5-naphthyridines asJournal of medicinal chemistry · 2025Article
- The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound.Nature microbiology · 2025Article
- PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum.Nature communications · 2025Article
- In Silico Screening ofBiologics : targets & therapy · 2025Article
- The artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular quiescence/senescence and drug resilience.Nature communications · 2024Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
- Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite.PLoS pathogens · 2023Article
- How many kinases are druggable? A review of our current understanding.The Biochemical journal · 2023Article
- Hsp90 and Associated Co-Chaperones of the Malaria Parasite.Biomolecules · 2022Review
- Update and elucidation ofComputational and structural biotechnology journal · 2022Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNovel antimalarials should be effective across all species of malaria parasites that infect humans, especially the two species that bear the most impact, Plasmodium falciparum and Plasmodium vivax. Protein kinases encoded by pathogens, as well as host kinases required for survival of intracellular pathogens, carry considerable potential as targets for antimalarial intervention (Adderley et al. Trends Parasitol 37:508-524, 2021; Wei et al. Cell Rep Med 2:100423, 2021). To date, no comprehensive P. vivax kinome assembly has been conducted; and the P. falciparum kinome, first assembled in 2004, requires an update. The present study, aimed to fill these gaps, utilises a recently published structurally-validated multiple sequence alignment (MSA) of the human kinome (Modi et al. Sci Rep 9:19790, 2019). This MSA is used as a scaffold to assist the alignment of all protein kinase sequences from P. falciparum and P. vivax, and (where possible) their assignment to specific kinase groups/families.
resultsWe were able to assign six P. falciparum previously classified as OPK or 'orphans' (i.e. with no clear phylogenetic relation to any of the established ePK groups) to one of the aforementioned ePK groups. Direct phylogenetic comparison established that despite an overall high level of similarity between the P. falciparum and P. vivax kinomes, which will help in selecting targets for intervention, there are differences that may underlie the biological specificities of these species. Furthermore, we highlight a number of Plasmodium kinases that have a surprisingly high level of similarity with their human counterparts and therefore not well suited as targets for drug discovery.
conclusionsDirect comparison of the kinomes of Homo sapiens, P. falciparum and P. vivax sheds additional light on the previously documented divergence of many P. falciparum and P. vivax kinases from those of their human host. We provide the first direct kinome comparison between the phylogenetically distinct species of P. falciparum and P. vivax, illustrating the key similarities and differences which must be considered in the context of kinase-directed antimalarial drug discovery, and discuss the divergences and similarities between the human and Plasmodium kinomes to inform future searches for selective antimalarial intervention.
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