DNA topoisomerase type I (Leishmania species) (Topoisomerase I)

DNA topoisomerase type I from Leishmania species is an ATP-independent enzyme responsible for regulating DNA topology by introducing transient single-strand breaks (nicks) in double-stranded DNA, thereby relaxing supercoiling and enabling critical processes such as replication, transcription, recombination, and repair[1][4][5]. Unlike human topoisomerase I, Leishmania topoisomerase I is unusual in being a heterodimer composed of a large subunit (which binds DNA but is catalytically inert) and a small subunit containing the active site tyrosine within the SKXXY motif required for nucleophilic attack on DNA[2][3][5]. The enzyme is essential for parasite survival and is proposed as a promising therapeutic target for new antiparasitic drugs against leishmaniasis. Its structure, function, and inhibitor sensitivity differ from mammalian homologs, influencing ongoing drug discovery and selectivity optimization[1][2][3][4][5].

Other names

Topoisomerase I (Leishmania)LdTOP1 (for Leishmania donovani)DNA topoisomerase type IB (Leishmania donovani)DNA topoisomerase type IB large subunit (LdTOP1L)DNA topoisomerase type IB small subunit (LdTOP1S)

Inhibition of DNA relaxation and supercoiling release via stabilization of covalent enzyme-DNA intermediate (camptothecin and related ligands)