EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 5481, Year 2024
掲載日	2024年6月28日
著者	Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng /
PubMed 要旨	Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, ...Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.
リンク	Nat Commun / PubMed:38942792 / PubMed Central
手法	EM (単粒子)
解像度	2.0 - 3.6 Å
構造データ	36836 EMDBエントリ画像なし 8k2a EMDB-36836, PDB-8k2a: Cryo-EM structure of the human 55S mitoribosome with Tigecycline 手法: EM (単粒子) / 解像度: 2.9 Å 36837 EMDBエントリ画像なし 8k2b EMDB-36837, PDB-8k2b: Cryo-EM structure of the human 39S mitoribosome with Tigecycline 手法: EM (単粒子) / 解像度: 3.4 Å 36838 EMDBエントリ画像なし 8k2c EMDB-36838, PDB-8k2c: Cryo-EM structure of the human 80S ribosome with Tigecycline 手法: EM (単粒子) / 解像度: 2.4 Å 36839 EMDBエントリ画像なし 8k2d EMDB-36839, PDB-8k2d: Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A 手法: EM (単粒子) / 解像度: 3.2 Å 36945 EMDBエントリ画像なし 8k82 EMDB-36945, PDB-8k82: Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not5 and P-site tRNA 手法: EM (単粒子) / 解像度: 3.0 Å 38629 EMDBエントリ画像なし 8xsx EMDB-38629, PDB-8xsx: Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA, SERBP1 and eEF2 手法: EM (単粒子) / 解像度: 2.4 Å 38630 EMDBエントリ画像なし 8xsy EMDB-38630, PDB-8xsy: Cryo-EM structure of the human 80S ribosome with Tigecycline, e-tRNA and CCDC124 (40S head Swivelled) 手法: EM (単粒子) / 解像度: 3.0 Å 38631 EMDBエントリ画像なし 8xsz EMDB-38631, PDB-8xsz: Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA and P-tRNA 手法: EM (単粒子) / 解像度: 3.2 Å 38632 EMDBエントリ画像なし 8xt0 EMDB-38632, PDB-8xt0: Cryo-EM structure of the human 55S mitoribosome with 5um Tigecycline 手法: EM (単粒子) / 解像度: 3.2 Å 38633 EMDBエントリ画像なし 8xt1 EMDB-38633, PDB-8xt1: Cryo-EM structure of the human 39S mitoribosome with 5uM Tigecycline 手法: EM (単粒子) / 解像度: 3.1 Å 38634 EMDBエントリ画像なし 8xt2 EMDB-38634, PDB-8xt2: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline 手法: EM (単粒子) / 解像度: 3.3 Å 38635 EMDBエントリ画像なし 8xt3 EMDB-38635, PDB-8xt3: Cryo-EM structure of the human 39S mitoribosome with 10uM Tigecycline 手法: EM (単粒子) / 解像度: 3.1 Å EMDBエントリ画像なし EMDB-38636: Cryo-EM structure of the human 55S mitoribosome with 5uM Tigecycline (focusing on 39S ribosome) 手法: EM (単粒子) / 解像度: 3.1 Å EMDBエントリ画像なし EMDB-38637: Cryo-EM structure of the human 55S mitoribosome with 5uM Tigecycline (focusing on 28S ribosome head) 手法: EM (単粒子) / 解像度: 3.4 Å EMDBエントリ画像なし EMDB-38638: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline (focusing on 39S ribosome) 手法: EM (単粒子) / 解像度: 3.2 Å EMDBエントリ画像なし EMDB-38639: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline (focusing on 28S ribosome head) 手法: EM (単粒子) / 解像度: 3.6 Å 39455 EMDBエントリ画像なし 8yoo EMDB-39455, PDB-8yoo: Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline 手法: EM (単粒子) / 解像度: 2.0 Å 39456 EMDBエントリ画像なし 8yop EMDB-39456, PDB-8yop: Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline 手法: EM (単粒子) / 解像度: 2.2 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-T1C: TIGECYCLINE / 薬剤, 抗生剤YM ChemComp-ZN: Unknown entry ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP / GDP, エネルギー貯蔵分子YM ChemComp-PNS: 4'-PHOSPHOPANTETHEINE / パンテテイン4′-りん酸 ChemComp-SPD: SPERMIDINE / スペルミジン ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子*YM
由来	homo sapiens (ヒト) saccharomyces cerevisiae (パン酵母)
キーワード	RIBOSOME / 55S mitoribosome / Tigecycline / antibiotic / 39S mitoribosome / 80S ribosome / eEF2 / SERBP1 / CCDC124