Affinage · Plasmodium

PPRD

PF3D7_1455900 · polyprenol reductase

Annotated
2026-09-08
2 papers in source corpus 1 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPRD (PF3D7_1455900) is an active polyprenol reductase in Plasmodium falciparum that catalyzes the reduction of polyprenol to dolichol as a committed step in the parasite's dolichol biosynthesis pathway (PMID:32764679). Metabolomics profiling of intraerythrocytic stages established de novo biosynthesis of polyprenols and dolichols of 15–19 isoprene units and demonstrated that dolichol is produced via PPRD-mediated polyprenol reduction (PMID:32764679). Beyond this enzymatic assignment, no further mechanistic detail—structural model, catalytic residues, cofactor requirements, or protein partners—has been characterized for PPRD in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2020 Medium

    It was unknown whether P. falciparum synthesizes dolichol de novo and which enzyme performs the polyprenol-to-dolichol reduction; identifying PPRD as the responsible reductase established the enzymatic basis of parasite dolichol biosynthesis.

    Evidence Metabolomics lipid profiling combined with enzymatic activity confirmation in P. falciparum intraerythrocytic stages

    PMID:32764679

    Open questions at the time
    • No structural model, catalytic residues, or cofactor requirement defined for PPRD
    • Enzyme activity inferred from parasite lipid profiles rather than reconstituted with purified protein
    • No knockout/knockdown to establish essentiality or downstream glycosylation consequences
  2. 2020 Low

    Whether PPRD-dependent cis-polyisoprenoid production is constant or stage-specific was unresolved; distinct polyprenol/dolichol profiles across the asexual cycle and between asexual and gametocyte stages indicated developmental regulation of this pathway.

    Evidence Metabolomics profiling across P. falciparum developmental stages, with PPRD activity inferred from lipid profiles

    PMID:32764679

    Open questions at the time
    • PPRD activity inferred indirectly from lipid profiles rather than measured directly at each stage
    • Regulatory mechanism (transcriptional, post-translational) driving stage-specific activity unknown
    • Functional consequence of stage-specific dolichol levels not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The catalytic mechanism, cofactor dependence, structural basis, essentiality, and protein interaction context of PPRD remain uncharacterized.
  • No reconstitution with purified enzyme
  • No genetic essentiality data
  • No structural or interaction data

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
2020 PPRD (PF3D7_1455900) functions as an active polyprenol reductase in P. falciparum, catalyzing the reduction of polyprenol to dolichol as part of the dolichol biosynthesis pathway. Metabolomics profiling confirmed de novo biosynthesis of polyprenols and dolichols of 15–19 isoprene units and demonstrated that dolichol production occurs via polyprenol reduction by PfPPRD. Metabolomics profiling; enzymatic activity confirmation in P. falciparum intraerythrocytic stages Scientific reports Medium 32764679
2020 PPRD (PF3D7_1455900)-dependent dolichol biosynthesis in P. falciparum produces a distinctive polyprenol and dolichol profile that changes across the intraerythrocytic asexual cycle and between asexual and gametocyte stages, indicating that PPRD activity (and thus cis-polyisoprenoid biosynthesis) is developmentally regulated. Metabolomics profiling across parasite developmental stages Scientific reports Low 32764679

Source papers

Stage 0 corpus · 2 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum. Scientific reports 20 32764679
2023 Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite. Molecules (Basel, Switzerland) 1 38202761