DNA topoisomerase 2 (Plasmodium falciparum) (PfTopoII)

DNA topoisomerase 2 (Plasmodium falciparum) is an essential enzyme required for the survival and proliferation of the malaria parasite. It manages DNA topology by creating transient double-strand breaks to allow the passage of one DNA duplex through another, a process critical for DNA replication, transcription, and chromosome segregation during the parasite's erythrocytic cycle (UniProt Q8I168). Because the parasite undergoes rapid nuclear divisions, the activity of PfTopoII is indispensable for maintaining genomic integrity (PubMed: 15133153). As a therapeutic target, it is susceptible to various inhibitors, including epipodophyllotoxins and fluoroquinolones, which trap the enzyme in a covalent complex with DNA, leading to irreversible genomic damage and parasite death (PubMed: 22430957). However, the high degree of structural similarity between the Plasmodium enzyme and human topoisomerase II poses a significant challenge for drug design, as non-selective inhibition can lead to severe host toxicity, including bone marrow suppression and cardiotoxicity (PubMed: 25637551). Current research focuses on identifying parasite-specific pockets within the enzyme to develop selective antimalarial agents that bypass host isoforms.

Other names

Plasmodium DNA topoisomerase IIDNA topoisomerase IIPfTop2Type II DNA topoisomerase

Inhibition of DNA strand re-ligation, stabilization of the covalent enzyme-DNA cleavage complex, and induction of lethal double-strand breaks.