Affinage · Plasmodium

TOP6A

PF3D7_1217100 · DNA topoisomerase 6 subunit A

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1217100 (TOP6A/PfTopoVIA) is the A subunit of the P. falciparum type II topoisomerase VI complex, functioning in ATP-dependent DNA topology management (PMID:27303712). It heterodimerizes with PfTopoVIB, and only the combined PfTopoVIB-VIA complex — not PfTopoVIB alone — rescues the lethal phenotype of yeast Δtopo II mutants, establishing TOP6A as essential for functional type II topoisomerase complementation (PMID:27303712). Cell-free extracts containing the PfTopoVIB-VIA complex exhibit ATP- and Mg2+-dependent DNA decatenation activity that is abrogated by anti-PfTopoVIB antibody and inhibited by radicicol and etoposide but not by the gyrase inhibitor novobiocin (PMID:27303712). Beyond its membership in this heteromeric complex and the associated decatenation activity, no further mechanistic detail about PF3D7_1217100 has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2016 Medium

    It was unknown whether P. falciparum encodes a functional type II topoisomerase VI and what role the A subunit plays; this work established that PfTopoVIA (PF3D7_1217100) partners with PfTopoVIB to form a complex that is essential and sufficient for type II topoisomerase activity.

    Evidence Yeast two-hybrid interaction, genetic complementation of yeast Δtopo II mutants, cell-free ATP/Mg2+-dependent decatenation assay with antibody and inhibitor panels, in a heterologous S. cerevisiae system

    PMID:27303712

    Open questions at the time
    • No in vitro reconstitution with purified Plasmodium TOP6A protein; activity shown only in cell-free extracts
    • Catalytic contribution of TOP6A itself versus PfTopoVIB not separately dissected
    • Native localization, expression timing, and essentiality within P. falciparum blood-stage biology not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic catalytic role of TOP6A, its structure, and its function within intact P. falciparum parasites remain undefined.
  • No structural model of TOP6A or the PfTopoVIB-VIA complex
  • No reconstitution with purified recombinant TOP6A
  • No characterization of TOP6A localization or requirement in the native parasite

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
PFTOPOVIB
Complex memberships
PfTopoVIB-VIA type II topoisomerase VI complex

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 PF3D7_1217100 (PfTopoVIA) forms a heteromeric complex with PfTopoVIB as shown by yeast two-hybrid analysis. The PfTopoVIB-VIA complex (requiring both subunits) can rescue the lethal phenotype of yeast ΔtopoII mutants, whereas PfTopoVIB alone cannot, establishing that TOP6A (PfTopoVIA) is essential for functional complementation. Cell-free extracts containing the PfTopoVIB-VIA complex exhibit ATP- and Mg2+-dependent decatenation activity, and this activity is specifically abrogated by anti-PfTopoVIB antibody. Radicicol and etoposide inhibit this decatenation activity, whereas the gyrase inhibitor novobiocin does not. Yeast two-hybrid (protein-protein interaction); heterologous expression in Saccharomyces cerevisiae; genetic complementation of yeast ΔtopoII mutants; cell-free decatenation assay; antibody inhibition; pharmacological inhibitor panel mSphere Medium 27303712

Source papers

Stage 0 corpus · 6 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Purification and characterization of Plasmodium berghei DNA topoisomerases I and II: drug action, inhibition of decatenation and relaxation, and stimulation of DNA cleavage. Biochemistry 77 3011062
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
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
2016 Radicicol-Mediated Inhibition of Topoisomerase VIB-VIA Activity of the Human Malaria Parasite Plasmodium falciparum. mSphere 20 27303712