Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

ABSTRACT: Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and cl

SUBMITTER: Piton J 

PROVIDER: S-EPMC2923608 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature