Structural basis of topoisomerase targeting by delafloxacin.

ABSTRACT: Delafloxacin is a potent anionic fluoroquinolone approved for the treatment of respiratory infections that acts by trapping the DNA cleavage complexes of bacterial topoisomerase IV and gyrase. Its N-1-pyridinyl-, C-7-azetidinyl- and C-8-chlorine substituents confer enhanced antibiotic activity against bacteria resistant to other fluoroquinolones, but its mode of action is unclear. Here we present the X-ray crystal structures of a delafloxacin-DNA cleavage complex obtained by co-crystallization with Streptococcus pneumoniae topo IV using a graphene nucleant and solved at 2.0 and 2.4 Å resolution. The two Mg²⁺-chelated delafloxacin molecules intercalated at the DNA cleavage site are bound in an unusual conformation involving interacting out-of-plane N-1-aromatic- and C-8-chlorine-

SUBMITTER: Najmudin S 

PROVIDER: S-EPMC12217528 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature