6CAE

Crystal structure of the Thermus thermophilus 70S ribosome in complex with NOSO-95179 antibiotic and bound to mRNA and A-, P- and E-site tRNAs at 2.6A resolution

This is a non-PDB format compatible entry.

Summary for 6CAE

• Entry DOI: 10.2210/pdb6cae/pdb
• Related PRD ID: PRD_002546
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• Functional Keywords: noso-95179, odilorhabdin, antibiotic, inhibitor, ribosome, 70s, ribosome structure, inhibition of translation, decoding center, ribosome-inhibitor complex, ribosome/inhibitor
• Biological source: Escherichia coli; More
• Total number of polymer chains: 115
• Total formula weight: 4576003.21

Authors

Pantel, L.,Florin, T.,Dobosz-Bartoszek, M.,Racine, E.,Sarciaux, M.,Serri, M.,Houard, J.,Campagne, J.M.,Marcia de Figueiredo, R.,Midrier, C.,Gaudriault, S.,Givaudan, A.,Lanois, A.,Forst, S.,Aumelas, A.,Cotteaux-Lautard, C.,Bolla, J.M.,Vingsbo Lundberg, C.,Huseby, D.,Hughes, D.,Villain-Guillot, P.,Mankin, A.S.,Polikanov, Y.S.,Gualtieri, M. (deposition date: 2018-01-30, release date: 2018-04-18, Last modification date: 2025-03-19)

Primary citation

Pantel, L.,Florin, T.,Dobosz-Bartoszek, M.,Racine, E.,Sarciaux, M.,Serri, M.,Houard, J.,Campagne, J.M.,de Figueiredo, R.M.,Midrier, C.,Gaudriault, S.,Givaudan, A.,Lanois, A.,Forst, S.,Aumelas, A.,Cotteaux-Lautard, C.,Bolla, J.M.,Vingsbo Lundberg, C.,Huseby, D.L.,Hughes, D.,Villain-Guillot, P.,Mankin, A.S.,Polikanov, Y.S.,Gualtieri, M.
Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site.
Mol. Cell, 70:83-94.e7, 2018

PubMed Abstract: Growing resistance of pathogenic bacteria and shortage of antibiotic discovery platforms challenge the use of antibiotics in the clinic. This threat calls for exploration of unconventional sources of antibiotics and identification of inhibitors able to eradicate resistant bacteria. Here we describe a different class of antibiotics, odilorhabdins (ODLs), produced by the enzymes of the non-ribosomal peptide synthetase gene cluster of the nematode-symbiotic bacterium Xenorhabdus nematophila. ODLs show activity against Gram-positive and Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae, and can eradicate infections in animal models. We demonstrate that the bactericidal ODLs interfere with protein synthesis. Genetic and structural analyses reveal that ODLs bind to the small ribosomal subunit at a site not exploited by current antibiotics. ODLs induce miscoding and promote hungry codon readthrough, amino acid misincorporation, and premature stop codon bypass. We propose that ODLs' miscoding activity reflects their ability to increase the affinity of non-cognate aminoacyl-tRNAs to the ribosome.

PubMed: 29625040
DOI: 10.1016/j.molcel.2018.03.001

Experimental method

X-RAY DIFFRACTION (2.6 Å)