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

これはPDB形式変換不可エントリーです。

6CFK の概要

• エントリーDOI: 10.2210/pdb6cfk/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• 機能のキーワード: chloramphenicol, antibiotic, inhibitor, ribosome, 70s, ribosome structure, inhibition of translation, peptidyl transferase center, ribosome-inhibitor complex, ribosome/inhibitor
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 106
• 化学式量合計: 4423447.16

構造登録者

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. (登録日: 2018-02-15, 公開日: 2018-03-07, 最終更新日: 2025-03-19)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)