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Updated: May 21, 2026

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses
Published on: February 25, 2011
Dual site targeting of the bacterial 70S ribosome by tetracyclines
Swapnil C Devarkar1, Ivan B Lomakin2,3, Jimin Wang1
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Abstract:
The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S subunit of the bacterial ribosome. Among the tested tetracyclines, Doxycycline was distinct in its ability to dimerize and bind the NPET at multiple locations. Structural comparison of Doxycycline, Minocycline, and Sarecycline bound to the Escherichia coli and Cutibacterium acnes 70S ribosome revealed species-specific differences affecting drug interaction and occupancy. Our results reveal a dual site mechanism of action for tetracyclines and provide a structural basis for rational design of narrow spectrum tetracyclines to overcome the rising threat of antibiotic resistance.
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