9PIJ

E. coli 70S ribosome bound to Minocycline

This is a non-PDB format compatible entry.

Summary for 9PIJ

• Entry DOI: 10.2210/pdb9pij/pdb
• EMDB information: 71669
• Descriptor: 50S ribosomal protein L33, Small ribosomal subunit protein uS5, Small ribosomal subunit protein bS6, ... (59 entities in total)
• Functional Keywords: tetracycline, bacterial ribosome, protein translation, minocycline, antibiotic, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 54
• Total formula weight: 2186882.88

Authors

Devarkar, S.C.,Lomakin, I.B.,Bunick, C.G. (deposition date: 2025-07-10, release date: 2026-05-13, Last modification date: 2026-06-03)

Primary citation

Devarkar, S.C.,Lomakin, I.B.,Wang, J.,Grada, A.,Bunick, C.G.
Dual site targeting of the bacterial 70S ribosome by tetracyclines.
Nat Commun, 17:-, 2026

PubMed 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.

PubMed: 42156748
DOI: 10.1038/s41467-026-72788-9

Experimental method

ELECTRON MICROSCOPY (2.2 Å)