DNA topoisomerase 1 (Leishmania) (LdTOP1) (LdTOP1)

DNA topoisomerase 1 (Leishmania) is a critical enzyme involved in maintaining DNA topology during essential cellular processes such as replication, transcription, and recombination within the Leishmania parasite (PubMed: 15591301). Unlike the monomeric Type IB topoisomerases found in higher eukaryotes, the Leishmania version is a unique heterodimer composed of large and small subunits, which presents a significant structural difference for selective drug targeting (UniProt: A0A0L1K064). Amarogentin, a secoiridoid glycoside derived from the medicinal plant Swertia chirata, acts as a potent inhibitor of this enzyme (PubMed: 8663219). By stabilizing the covalent intermediate between the enzyme and DNA, amarogentin prevents the religation of DNA strands, leading to the accumulation of DNA breaks and subsequent apoptosis-like death of the parasite (PubMed: 10449214). This interaction makes the enzyme a primary target for developing novel antileishmanial therapies, particularly for visceral leishmaniasis.

Other names

Leishmania donovani DNA topoisomerase ILdTOP1LSType IB topoisomeraseDNA topoisomerase I large subunitDNA topoisomerase I small subunit

Inhibition of DNA topoisomerase I activity by stabilizing the enzyme-DNA covalent complex (cleavable complex), preventing DNA religation and inducing apoptosis-like cell death in the parasite.