Cryo-EM structure of the full-length Mycobacterium tuberculosis DNA Gyrase nucleoprotein complexes

DNA Gyrase is an essential enzyme involved in the homeostatic control of DNA supercoiling and the target of successful antibacterial compounds. In Mycobacterium tuberculosis (Mtb), DNA Gyrase is the unique topo IIA topoisomerase and thus the unique target of FQ, the second line antibiotics used in TB treatment. Recently we determined the first crystal structures of a CTD-truncated Mtb gyrase at high resolution (Petrella et al., 2019). This work highlighted the role of a particular domain insertion specific to this gyrase but despite extensive studies, the detailed architecture of the full-length enzyme is still lacking and thus the molecular specificities and conformational intermediates of this highly flexible macromolecule. High- resolution cryo-EM data will enable the visualization of the binding pockets of the inhibitory molecules and will open perspectives for targeting conformational intermediates.