5VP2

Crystal structure of the Thermus thermophilus 70S ribosome in complex with madumycin II and bound to mRNA and A-, P- and E-site tRNAs at 2.8A resolution

これはPDB形式変換不可エントリーです。

5VP2 の概要

• エントリーDOI: 10.2210/pdb5vp2/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: madumycin ii, streptogramin a, antibiotic, ribosome inhibitor, 70s ribosome, ribosome structure, inhibition of translation, peptidyl transferase center, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4571576.15

構造登録者

Osterman, I.A.,Khabibullina, N.F.,Komarova, E.S.,Kasatsky, P.,Kartsev, V.G.,Bogdanov, A.A.,Dontsova, O.A.,Konevega, A.L.,Sergiev, P.V.,Polikanov, Y.S. (登録日: 2017-05-04, 公開日: 2017-06-28, 最終更新日: 2025-03-12)

主引用文献

Osterman, I.A.,Khabibullina, N.F.,Komarova, E.S.,Kasatsky, P.,Kartsev, V.G.,Bogdanov, A.A.,Dontsova, O.A.,Konevega, A.L.,Sergiev, P.V.,Polikanov, Y.S.
Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state.
Nucleic Acids Res., 45:7507-7514, 2017

PubMed Abstract: The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

PubMed: 28505372
DOI: 10.1093/nar/gkx413

実験手法

X-RAY DIFFRACTION (2.8 Å)