Affinage · Plasmodium

DDI1

PF3D7_1409300 · DNA damage-inducible protein 1

Annotated
2026-09-08
7 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1409300 (DDI1) is a DNA damage-inducible protein of Plasmodium falciparum implicated in the parasite's DNA damage response: genome-wide transcriptional profiling after methyl methanesulphonate treatment placed DDI1 among DNA repair genes whose expression is induced in wild-type parasites but fails to be induced in mutator strains (Dd2, W2) carrying point mutations in DNA repair genes (PMID:27033103). DDI1 is described as functioning within the ubiquitin-proteasome system associated with the unfolded protein response, and computational docking indicates artemisinin and its derivatives bind three loop regions of the protein (PMID:40113723). Beyond this transcriptional and computational evidence, the direct enzymatic activity, molecular partners, and mechanism of PF3D7_1409300 have not been characterized by rigorous experimental studies in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2016 Low

    To learn which parasite genes constitute the DNA damage response, transcriptional profiling after DNA-damaging treatment tested whether DDI1 is part of the repair network, establishing its inducibility as a DNA damage-responsive gene.

    Evidence Genome-wide DNA microarray profiling after MMS treatment, with genome sequencing of mutator strains (Dd2, W2) to identify DNA repair gene mutations

    PMID:27033103

    Open questions at the time
    • Transcriptional inference only; no direct assay of DDI1 protein activity
    • Does not establish DDI1's biochemical role in repair
    • Single lab, single method
  2. 2025 Low

    To assess DDI1 as an antimalarial drug target, computational modeling asked whether artemisinin and derivatives engage the protein, identifying three candidate loop-binding sites and framing DDI1 within the ubiquitin-proteasome/unfolded protein response system.

    Evidence Molecular docking and molecular dynamics simulation of artemisinin derivatives against PfDdi1, referencing prior in vitro inhibition data

    PMID:40113723

    Open questions at the time
    • Computational prediction only; no mutagenesis or structural validation in this study
    • Referenced in vitro inhibition data not described in detail here
    • Direct enzymatic activity of DDI1 not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct enzymatic mechanism, physiological substrates, and molecular interaction partners of PF3D7_1409300 remain uncharacterized by direct experimental evidence.
  • No biochemical demonstration of DDI1 enzymatic activity
  • No validated protein interaction partners in the corpus
  • No structural or genetic knockout data defining function

Mechanism profile

Synthesis pass · controlled-vocabulary classification
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 P. falciparum DDI1 (PF3D7_1409300) is implicated in the DNA damage response; genome-wide transcriptional profiling after MMS-induced DNA damage provided evidence that DDI1 is among the DNA repair genes whose expression is induced in wild-type parasites but fails to be induced in mutator strains (Dd2, W2) carrying point mutations in DNA repair genes, placing DDI1 within the parasite's double-strand break and excision repair response network. Genome-wide transcriptional profiling (DNA microarray) after methyl methanesulphonate (MMS) treatment; genome sequencing of mutator strains to identify point mutations in DNA repair genes Scientific reports Low 27033103
2025 Computational modeling indicates that artemisinin (ART) and its derivatives (artemether, arteether, artemiside, artesunate) bind to PfDdi1 (PF3D7_1409300) at three key loops (Loop 1: GLN266–ILE269; Loop 2: ILE323–TYR326; Loop 3: ALA292–GLY294), with free binding energies ranging from −20.75 kcal/mol (AET) to −34.24 kcal/mol (ATS); the abstract also references prior in vitro studies showing ART and dihydroartemisinin inhibit PfDdi1 activity, suggesting these loops are potential binding/inhibition sites. PfDdi1 is described as functioning in the ubiquitin-proteasome system (UPS) involved in the unfolded protein response. Computational molecular docking and molecular dynamics simulation; referenced in vitro inhibition assays (from prior studies, not this paper) Cell biochemistry and biophysics Low 40113723

Source papers

Stage 0 corpus · 7 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Rapid repeated DNA replication during microgametogenesis and DNA synthesis in young zygotes of Plasmodium berghei. Transactions of the Royal Society of Tropical Medicine and Hygiene 61 3088783
1987 Plasmodium species: flow cytometry and microfluorometry assessments of DNA content and synthesis. Experimental parasitology 57 2440713
2016 DNA damage regulation and its role in drug-related phenotypes in the malaria parasites. Scientific reports 56 27033103
1968 DNA, RNA , and protein synthesis in erythrocytic forms of Plasmodium knowlesi. The American journal of tropical medicine and hygiene 56 4971014
2005 DNA-[adenine] methylation in lower eukaryotes. Biochemistry. Biokhimiia 42 15948708
1987 From Laveran's discovery to DNA probes: new trends in diagnosis of malaria. Lancet (London, England) 31 2892060
2025 Computational Analysis of Plasmodium falciparum DNA Damage Inducible Protein 1 (PfDdi1): Insights into Binding of Artemisinin and its Derivatives and Implications for Antimalarial Drug Design. Cell biochemistry and biophysics 4 40113723