7MD7

Crystal structure of the Thermus thermophilus 70S ribosome in complex with triphenylphosphonium analog of chloramphenicol CAM-C4-TPP and protein Y (YfiA) at 2.80A resolution

これはPDB形式変換不可エントリーです。

7MD7 の概要

• エントリーDOI: 10.2210/pdb7md7/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• 機能のキーワード: chloramphenicol, antibiotic, 70s ribosome, translation inhibitor, peptidyl transferase center, nascent peptide exit tunnel, ribosome
• 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: 4428454.05

構造登録者

Chen, C.-W.,Pavlova, J.A.,Lukianov, D.A.,Tereshchenkov, A.G.,Makarov, G.I.,Khairullina, Z.Z.,Tashlitsky, V.N.,Paleskava, A.,Konevega, A.L.,Bogdanov, A.A.,Osterman, I.A.,Sumbatyan, N.V.,Polikanov, Y.S. (登録日: 2021-04-03, 公開日: 2021-04-21, 最終更新日: 2025-03-19)

主引用文献

Chen, C.W.,Pavlova, J.A.,Lukianov, D.A.,Tereshchenkov, A.G.,Makarov, G.I.,Khairullina, Z.Z.,Tashlitsky, V.N.,Paleskava, A.,Konevega, A.L.,Bogdanov, A.A.,Osterman, I.A.,Sumbatyan, N.V.,Polikanov, Y.S.
Binding and Action of Triphenylphosphonium Analog of Chloramphenicol upon the Bacterial Ribosome.
Antibiotics, 10:-, 2021

PubMed Abstract: Chloramphenicol (CHL) is a ribosome-targeting antibiotic that binds to the peptidyl transferase center (PTC) of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving the properties of this inhibitor, we explored ribosome binding and inhibitory properties of a semi-synthetic triphenylphosphonium analog of CHL-CAM-C4-TPP. Our data demonstrate that this compound exhibits a ~5-fold stronger affinity for the bacterial ribosome and higher potency as an in vitro protein synthesis inhibitor compared to CHL. The X-ray crystal structure of the 70S ribosome in complex with CAM-C4-TPP reveals that, while its amphenicol moiety binds at the PTC in a fashion identical to CHL, the C4-TPP tail adopts an extended propeller-like conformation within the ribosome exit tunnel where it establishes multiple hydrophobic Van der Waals interactions with the rRNA. The synthesized compound represents a promising chemical scaffold for further development by medicinal chemists because it simultaneously targets the two key functional centers of the bacterial ribosome-PTC and peptide exit tunnel.

PubMed: 33916420
DOI: 10.3390/antibiotics10040390

実験手法

X-RAY DIFFRACTION (2.8 Å)