5JC9

Structure of the Escherichia coli ribosome with the U1052G mutation in the 16S rRNA

This is a non-PDB format compatible entry.

Summary for 5JC9

• Entry DOI: 10.2210/pdb5jc9/pdb
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (69 entities in total)
• Functional Keywords: negamycin, tetracycline, u1052g, resistance, antibiotics, ribosome
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 105
• Total formula weight: 4271005.10

Authors

Cocozaki, A.,Ferguson, A. (deposition date: 2016-04-14, release date: 2016-07-06, Last modification date: 2016-08-03)

Primary citation

Cocozaki, A.I.,Altman, R.B.,Huang, J.,Buurman, E.T.,Kazmirski, S.L.,Doig, P.,Prince, D.B.,Blanchard, S.C.,Cate, J.H.,Ferguson, A.D.
Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors.
Proc.Natl.Acad.Sci.USA, 113:8188-8193, 2016

PubMed Abstract: Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future.

PubMed: 27382179
DOI: 10.1073/pnas.1605127113

Experimental method

X-RAY DIFFRACTION (3.03 Å)