DNA topoisomerase I (Mycobacterium tuberculosis) (MtTOP1)

DNA topoisomerase I from Mycobacterium tuberculosis (MtTOP1) is an essential enzyme responsible for resolving DNA supercoiling during critical processes including replication, transcription, recombination, and repair[1][3][5][9]. It is the only type IA topoisomerase in M. tuberculosis, required for growth and viability, and is validated as a promising therapeutic target for new anti-tubercular drugs, including treatment of strains resistant to conventional agents[1][2][3][7][9]. MtTOP1 functions by cutting and rejoining a single strand of DNA to modulate topological state, with unique structural features and a domain organization distinct from its bacterial counterparts[1][5][9]. Several gold(III) compounds and emerging small molecule inhibitors have demonstrated potent, selective inhibition of MtTOP1, offering a novel therapeutic strategy for tuberculosis, including multidrug-resistant cases[2][3][7]. Selectivity against the mycobacterial enzyme and minimized effects on mammalian topoisomerases are critical for therapeutic safety[2][3].

Other names

Mycobacterial DNA topoisomerase IMycobacterium tuberculosis topoisomerase ITopA (Mt)Type IA topoisomerase (Mycobacterium)

Catalytic inhibition of DNA cleavage and religation; Poisoning/stabilization of DNA cleavage complex