ArticleMolecular microbiology2015
Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle.
Article in Molecular microbiology, 2015. 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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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial.Frontiers in immunology · 2023Trial
- Therapeutic Targeting and Role of Cysteine Proteases in the Life Cycle of Malaria Parasite.Current medicinal chemistry · 2025Review
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
- Article
- The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates forBiomolecules · 2024Review
- Formation of ER-lumenal intermediates during export of Plasmodium proteins containing transmembrane-like hydrophobic sequences.PLoS pathogens · 2023Article
- The Nϵ-Rule for Serine, but Not Cysteine Catalytic Triads.Angewandte Chemie (International ed. in English) · 2022Article
- African-specific polymorphisms inFrontiers in cellular and infection microbiology · 2022Article
- Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.The EMBO journal · 2021Article
- Assessment of MixedCancers · 2021Article
- Malaria parasite egress at a glance.Journal of cell science · 2021Review
- Article
- The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion.eLife · 2020Article
- Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen.Protein science : a publication of the Protein Society · 2020Article
- A lipocalin mediates unidirectional heme biomineralization in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Characteristic features of the SERA multigene family in the malaria parasite.Parasites & vectors · 2020Review
- Simultaneous multiple allelic replacement in the malaria parasite enables dissection of PKG function.Life science alliance · 2020Article
- A malaria parasite subtilisin propeptide-like protein is a potent inhibitor of the egress protease SUB1.The Biochemical journal · 2020Article
- A pan-apicomplexan phosphoinositide-binding protein acts in malarial microneme exocytosis.EMBO reports · 2019Article
- Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery.PLoS biology · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The malaria parasite Plasmodium falciparum replicates in an intraerythrocytic parasitophorous vacuole (PV). The most abundant P. falciparum PV protein, called SERA5, is essential in blood stages and possesses a papain-like domain, prompting speculation that it functions as a proteolytic enzyme. Unusually however, SERA5 possesses a Ser residue (Ser596) at the position of the canonical catalytic Cys of papain-like proteases, and the function of SERA5 or whether it performs an enzymatic role is unknown. In this study, we failed to detect proteolytic activity associated with the Ser596-containing parasite-derived or recombinant protein. However, substitution of Ser596 with a Cys residue produced an active recombinant enzyme with characteristics of a cysteine protease, demonstrating that SERA5 can bind peptides. Using targeted homologous recombination in P. falciparum, we substituted Ser596 with Ala with no phenotypic consequences, proving that SERA5 does not perform an essential enzymatic role in the parasite. We could also replace an internal segment of SERA5 with an affinity-purification tag. In contrast, using almost identical targeting constructs, we could not truncate or C-terminally tag the SERA5 gene, or replace Ser596 with a bulky Arg residue. Our findings show that SERA5 plays an indispensable but non-enzymatic role in the P. falciparum blood-stage life cycle.
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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.