- EMDB-20121: Structure of trans-translation inhibitor bound to E. coli 70S rib... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-20121
タイトル
Structure of trans-translation inhibitor bound to E. coli 70S ribosome with P site tRNA
マップデータ
unfiltered main map
試料
複合体: Structure of trans-translation inhibitor bound to E. coli 70S ribosome with P site tRNA
複合体: 50S subunit
RNA: x 2種
タンパク質・ペプチド: x 29種
複合体: 30S subunit
RNA: x 3種
タンパク質・ペプチド: x 20種
リガンド: x 1種
機能・相同性
機能・相同性情報
positive regulation of ribosome biogenesis / DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / regulation of cell growth / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / ribosome binding ...positive regulation of ribosome biogenesis / DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / regulation of cell growth / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / ribosome binding / small ribosomal subunit / small ribosomal subunit rRNA binding / transferase activity / 5S rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / tRNA binding / cytoplasmic translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / zinc ion binding / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能
Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L31 type A / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein S21 ...Ribosomal protein S21, conserved site / Ribosomal protein S21 signature. / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L31 type A / Ribosomal protein S21 superfamily / Ribosomal protein S21 / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein S21 / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L16 signature 1. / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L9 signature. / Ribosomal protein L9, bacteria/chloroplast / Ribosomal protein L9, C-terminal / Ribosomal protein L9, C-terminal domain / Ribosomal protein L9, C-terminal domain superfamily / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L36 signature. / Ribosomal protein L28/L24 superfamily / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9 / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / Ribosomal protein L28 / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L5, bacterial-type / Ribosomal protein S14/S29 / Ribosomal protein L6, bacterial-type / Ribosomal protein L18, bacterial-type / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein S3, bacterial-type / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein S19, bacterial-type / Ribosomal protein L20 signature. / Ribosomal protein L9/RNase H1, N-terminal / Ribosomal protein S7, bacterial/organellar-type / Ribosomal protein S11, bacterial-type / Ribosomal protein L27, conserved site / Ribosomal protein S13, bacterial-type / Ribosomal protein L27 signature. / Ribosomal protein S20 / Ribosomal protein S20 superfamily / Ribosomal protein S20 / Ribosomal protein S9, bacterial/plastid / Ribosomal protein S4, bacterial-type / 30S ribosomal protein S17 / Ribosomal protein S5, bacterial-type / Ribosomal protein L14P, bacterial-type / Ribosomal protein L34, conserved site / Ribosomal protein L34 signature. / Ribosomal protein S6, plastid/chloroplast / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein S2, bacteria/mitochondria/plastid / Ribosomal protein L35 / Ribosomal L28 family / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L28/L24 / Ribosomal protein L33 superfamily / Ribosomal protein L30, bacterial-type / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / Ribosomal protein L16 / Ribosomal protein S18, conserved site / Ribosomal protein S18 signature. / L28p-like / Ribosomal protein S16 / Ribosomal protein S16 / Ribosomal protein L20 / Ribosomal protein S16 domain superfamily / Ribosomal protein L20 / Ribosomal protein L20, C-terminal / Ribosomal protein S15, bacterial-type / Ribosomal protein L21 / Ribosomal protein L27 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / : / Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / 30S ribosomal protein S7 / Large ribosomal subunit protein bL20 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein bL34 ...Large ribosomal subunit protein uL15 / : / Small ribosomal subunit protein bS18 / Large ribosomal subunit protein bL36 / Small ribosomal subunit protein bS21 / 30S ribosomal protein S7 / Large ribosomal subunit protein bL20 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS3 / Large ribosomal subunit protein bL34 / Small ribosomal subunit protein bS16 / 50S ribosomal protein L23 / Large ribosomal subunit protein bL25 / 50S ribosomal protein L35 / 30S ribosomal protein S10 / 50S ribosomal protein L4 / 30S ribosomal protein S19 / 50S ribosomal protein L22 / 50S ribosomal protein L29 / 30S ribosomal protein S17 / 50S ribosomal protein L14 / 50S ribosomal protein L24 / 50S ribosomal protein L5 / 30S ribosomal protein S14 / 30S ribosomal protein S8 / 50S ribosomal protein L6 / 50S ribosomal protein L18 / 30S ribosomal protein S5 / 50S ribosomal protein L30 / 30S ribosomal protein S4 / 50S ribosomal protein L33 / 30S ribosomal protein S20 / 30S ribosomal protein S15 / 50S ribosomal protein L21 / 30S ribosomal protein S9 / 50S ribosomal protein L13 / 50S ribosomal protein L31 / 50S ribosomal protein L32 / 50S ribosomal protein L9 / 30S ribosomal protein S2 / 50S ribosomal protein L19 / 30S ribosomal protein S13 / 30S ribosomal protein S12 / Small ribosomal subunit protein bS6 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL3 / 50S ribosomal protein L28 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM093278
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM121650
米国
引用
ジャーナル: Nat Commun / 年: 2021 タイトル: trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo. 著者: Zachary D Aron / Atousa Mehrani / Eric D Hoffer / Kristie L Connolly / Pooja Srinivas / Matthew C Torhan / John N Alumasa / Mynthia Cabrera / Divya Hosangadi / Jay S Barbor / Steven C ...著者: Zachary D Aron / Atousa Mehrani / Eric D Hoffer / Kristie L Connolly / Pooja Srinivas / Matthew C Torhan / John N Alumasa / Mynthia Cabrera / Divya Hosangadi / Jay S Barbor / Steven C Cardinale / Steven M Kwasny / Lucas R Morin / Michelle M Butler / Timothy J Opperman / Terry L Bowlin / Ann Jerse / Scott M Stagg / Christine M Dunham / Kenneth C Keiler / 要旨: Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not ...Bacterial ribosome rescue pathways that remove ribosomes stalled on mRNAs during translation have been proposed as novel antibiotic targets because they are essential in bacteria and are not conserved in humans. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibit trans-translation, the main ribosome rescue pathway in bacteria. Here, we report optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles, producing MBX-4132, which clears multiple-drug resistant Neisseria gonorrhoeae infection in mice after a single oral dose. Single particle cryogenic-EM studies of non-stop ribosomes show that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein bL27, suggesting a novel mechanism for specific inhibition of trans-translation by these molecules. These results show that trans-translation is a viable therapeutic target and reveal a new conformation within the bacterial ribosome that may be critical for ribosome rescue pathways.
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281.15 K / 装置: FEI VITROBOT MARK IV / 詳細: Blot time: 3.5 seconds.
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電子顕微鏡法
顕微鏡
FEI TITAN KRIOS
撮影
フィルム・検出器のモデル: DIRECT ELECTRON DE-64 (8k x 8k) 検出モード: COUNTING / デジタル化 - サイズ - 横: 4096 pixel / デジタル化 - サイズ - 縦: 4096 pixel / デジタル化 - サンプリング間隔: 6.5 µm / デジタル化 - 画像ごとのフレーム数: 1-78 / 撮影したグリッド数: 2 / 実像数: 2197 / 平均露光時間: 19.302 sec. / 平均電子線量: 58.0 e/Å2 詳細: Two separate datesets were combined. The imaging parameter was the same for both datasets. Firth data-set had 1752 micrographs. Second data-set had 445 micrographs.