Negamycin induces translational stalling and miscoding by binding to the small subunit head domain of the Escherichia coli ribosome.

ABSTRACT: Negamycin is a natural product with broad-spectrum antibacterial activity and efficacy in animal models of infection. Although its precise mechanism of action has yet to be delineated, negamycin inhibits cellular protein synthesis and causes cell death. Here, we show that single point mutations within 16S rRNA that confer resistance to negamycin are in close proximity of the tetracycline binding site within helix 34 of the small subunit head domain. As expected from its direct interaction with this region of the ribosome, negamycin was shown to displace tetracycline. However, in contrast to tetracycline-class antibiotics, which serve to prevent cognate tRNA from entering the translating ribosome, single-molecule fluorescence resonance energy transfer investigations revealed that negamycin

SUBMITTER: Olivier NB 

PROVIDER: S-EPMC4246262 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature