Inhibition of DNA cleavage and strand passage activities of Mycobacterium tuberculosis topoisomerase I.

ABSTRACT: Topoisomerase I (TopoI) is the sole DNA relaxase in Mycobacterium tuberculosis. Despite being a validated drug target and indispensable to the pathogen, only a limited repertoire of inhibitors targeting the enzyme have been identified. We employed monoclonal antibodies (mAbs) to address this shortfall. From the pool of a large number of mAbs, we describe an inhibitory mAb specific to mycobacterial TopoI with a distinct mechanism of action. Among the various steps of the TopoI reaction cycle, the mAb does not interfere with DNA binding but impedes DNA cleavage. It does not alter the religation activity of TopoI; however, it inhibits its strand passage activity. Probing with the mAb, we show the precise step at which the topology of the DNA is changed during DNA relaxation reaction. Surprisi

SUBMITTER: Faheem I 

PROVIDER: S-EPMC12449047 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature