TOP6B

PF3D7_1365600 (TOP6B) is the B subunit of the Plasmodium falciparum type II topoisomerase VI, functioning in ATP-dependent DNA decatenation (PMID:27303712). It self-associates into homodimers and heterodimerises with the A subunit (TOP6A), and only the assembled TOP6B–TOP6A complex reconstitutes type II topoisomerase activity: the complex decatenates DNA in an ATP- and Mg2+-dependent manner and rescues the lethality of yeast ΔtopoII mutants, whereas TOP6B alone is catalytically inactive and cannot complement (PMID:27303712). Anti-TOP6B antibody abrogates decatenation, and the activity is inhibited by radicicol and etoposide but not by the gyrase inhibitor novobiocin (PMID:27303712). Beyond this heterodimeric decatenation function established for the recombinant/heterologous system in (PMID:27303712), no further mechanistic detail—structure, in vitro reconstitution with purified protein, or in-parasite phenotype—has been characterized for PF3D7_1365600 in the available corpus.

1. 2016 Medium

   Whether PF3D7_1365600 encodes a functional topoisomerase subunit and how it partners with the A subunit was unknown; this work established TOP6B as a homodimer-forming, A-subunit-dependent component of an active type II topoisomerase.

   Evidence Yeast two-hybrid interaction mapping, ΔtopoII complementation epistasis, and cell-free ATP/Mg2+-dependent decatenation assay with antibody and drug inhibition in P. falciparum-derived subunits

   PMID:27303712

   Open questions at the time

   • No in vitro reconstitution with purified recombinant TOP6B protein
   • The catalytic contribution of TOP6B versus TOP6A within the complex is not dissected
   • No in-parasite genetic essentiality or knockout phenotype for PF3D7_1365600
2. 1986 Low

   Before gene-level identification, the question was whether Plasmodium possesses a eukaryotic-type topoisomerase II activity and whether antimalarials target it; a two-subunit, ATP/Mg2+-dependent activity was purified from P. berghei but was not attributed to any specific gene.

   Evidence Biochemical purification from P. berghei-infected erythrocytes with relaxation/unknotting/decatenation/catenation and drug inhibition assays

   PMID:3011062

   Open questions at the time

   • The purified subunits were not mapped to TOP6B at the gene level, so this activity cannot be assigned to PF3D7_1365600
   • Performed in P. berghei, not P. falciparum
   • No molecular identity of the ~160 kDa subunits established

• Whether TOP6B contributes catalytically or structurally within the heterodimer, its atomic structure, and its role in parasite replication in vivo remain open.
• No structural model of TOP6B or the TOP6B–TOP6A complex
• No in vitro reconstitution with fully purified recombinant subunits
• No genetic dissection of TOP6B function during the P. falciparum life cycle