6ND5

Crystal structure of the Thermus thermophilus 70S ribosome in complex with chloramphenicol and bound to mRNA and A-, P-, and E-site tRNAs at 2.60A resolution

This is a non-PDB format compatible entry.

Summary for 6ND5

• Entry DOI: 10.2210/pdb6nd5/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• Functional Keywords: chloramphenicol, erythromycin, competition, antibiotic, 70s ribosome, inhibition of translation, peptidyl transferase center, nascent peptide exit tunnel, ribosome, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Total number of polymer chains: 112
• Total formula weight: 4571677.03

Authors

Svetlov, M.S.,Plessa, E.,Chen, C.-W.,Bougas, A.,Krokidis, M.G.,Dinos, G.P.,Polikanov, Y.S. (deposition date: 2018-12-13, release date: 2019-03-20, Last modification date: 2023-11-15)

Primary citation

Svetlov, M.S.,Plessa, E.,Chen, C.W.,Bougas, A.,Krokidis, M.G.,Dinos, G.P.,Polikanov, Y.S.
High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition.
RNA, 25:600-606, 2019

PubMed Abstract: The 70S ribosome is a major target for antibacterial drugs. Two of the classical antibiotics, chloramphenicol (CHL) and erythromycin (ERY), competitively bind to adjacent but separate sites on the bacterial ribosome: the catalytic peptidyl transferase center (PTC) and the nascent polypeptide exit tunnel (NPET), respectively. The previously reported competitive binding of CHL and ERY might be due either to a direct collision of the two drugs on the ribosome or due to a drug-induced allosteric effect. Because of the resolution limitations, the available structures of these antibiotics in complex with bacterial ribosomes do not allow us to discriminate between these two possible mechanisms. In this work, we have obtained two crystal structures of CHL and ERY in complex with the 70S ribosome at a higher resolution (2.65 and 2.89 Å, respectively) allowing unambiguous placement of the drugs in the electron density maps. Our structures provide evidence of the direct collision of CHL and ERY on the ribosome, which rationalizes the observed competition between the two drugs.

PubMed: 30733327
DOI: 10.1261/rna.069260.118

Experimental method

X-RAY DIFFRACTION (2.6 Å)