6CFK

Crystal structure of the Thermus thermophilus 70S ribosome in complex with D-histidyl-CAM and bound to protein Y (YfiA) at 2.7A resolution

This is a non-PDB format compatible entry.

Summary for 6CFK

• Entry DOI: 10.2210/pdb6cfk/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• Functional Keywords: chloramphenicol, antibiotic, inhibitor, ribosome, 70s, ribosome structure, inhibition of translation, peptidyl transferase center, ribosome-inhibitor complex, ribosome/inhibitor
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 106
• Total formula weight: 4423447.16

Authors

Tereshchenkov, A.G.,Dobosz-Bartoszek, M.,Osterman, I.A.,Marks, J.,Sergeeva, V.A.,Kasatsky, P.,Komarova, E.S.,Stavrianidi, A.N.,Rodin, I.A.,Konevega, A.L.,Sergiev, P.V.,Sumbatyan, N.V.,Mankin, A.S.,Bogdanov, A.A.,Polikanov, Y.S. (deposition date: 2018-02-15, release date: 2018-03-07, Last modification date: 2025-03-19)

Primary citation

Tereshchenkov, A.G.,Dobosz-Bartoszek, M.,Osterman, I.A.,Marks, J.,Sergeeva, V.A.,Kasatsky, P.,Komarova, E.S.,Stavrianidi, A.N.,Rodin, I.A.,Konevega, A.L.,Sergiev, P.V.,Sumbatyan, N.V.,Mankin, A.S.,Bogdanov, A.A.,Polikanov, Y.S.
Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome.
J. Mol. Biol., 430:842-852, 2018

PubMed Abstract: Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino acid analogs of CHL. The L-histidyl analog binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogs were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL. However, the inhibitory properties of the semi-synthetic CHL analogs did not correlate with their affinity and in general, the amino acid analogs of CHL were less active inhibitors of translation in comparison with the original antibiotic. The X-ray crystal structures of the Thermus thermophilus 70S ribosome in complex with three semi-synthetic analogs showed that CHL derivatives bind at the peptidyl transferase center, where the aminoacyl moiety of the tested compounds established idiosyncratic interactions with rRNA. Although still fairly inefficient inhibitors of translation, the synthesized compounds represent promising chemical scaffolds that target the peptidyl transferase center of the ribosome and potentially are suitable for further exploration.

PubMed: 29410130
DOI: 10.1016/j.jmb.2018.01.016

Experimental method

X-RAY DIFFRACTION (2.7 Å)