+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6qul | ||||||
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タイトル | Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid | ||||||
要素 |
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キーワード | ANTIBIOTIC / ribosome / cadazolid / quinoxolidinone / 50S | ||||||
機能・相同性 | 機能・相同性情報 transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / mRNA regulatory element binding translation repressor activity ...transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / mRNA regulatory element binding translation repressor activity / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / regulation of cell growth / response to reactive oxygen species / DNA-templated transcription termination / response to radiation / ribosomal large subunit assembly / mRNA 5'-UTR binding / large ribosomal subunit / ribosome binding / transferase activity / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / tRNA binding / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / translation / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Escherichia coli (大腸菌) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3 Å | ||||||
データ登録者 | Scaiola, A. / Leibundgut, M. / Boehringer, D. / Ritz, D. | ||||||
引用 | ジャーナル: Sci Rep / 年: 2019 タイトル: Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic. 著者: Alain Scaiola / Marc Leibundgut / Daniel Boehringer / Patrick Caspers / Daniel Bur / Hans H Locher / Georg Rueedi / Daniel Ritz / 要旨: Oxazolidinones are synthetic antibiotics used for treatment of infections caused by Gram-positive bacteria. They target the bacterial protein synthesis machinery by binding to the peptidyl ...Oxazolidinones are synthetic antibiotics used for treatment of infections caused by Gram-positive bacteria. They target the bacterial protein synthesis machinery by binding to the peptidyl transferase centre (PTC) of the ribosome and interfering with the peptidyl transferase reaction. Cadazolid is the first member of quinoxolidinone antibiotics, which are characterized by combining the pharmacophores of oxazolidinones and fluoroquinolones, and it is evaluated for treatment of Clostridium difficile gastrointestinal infections that frequently occur in hospitalized patients. In vitro protein synthesis inhibition by cadazolid was shown in Escherichia coli and Staphylococcus aureus, including an isolate resistant against linezolid, the prototypical oxazolidinone antibiotic. To better understand the mechanism of inhibition, we determined a 3.0 Å cryo-electron microscopy structure of cadazolid bound to the E. coli ribosome in complex with mRNA and initiator tRNA. Here we show that cadazolid binds with its oxazolidinone moiety in a binding pocket in close vicinity of the PTC as observed previously for linezolid, and that it extends its unique fluoroquinolone moiety towards the A-site of the PTC. In this position, the drug inhibits protein synthesis by interfering with the binding of tRNA to the A-site, suggesting that its chemical features also can enable the inhibition of linezolid-resistant strains. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6qul.cif.gz | 1.9 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6qul.ent.gz | 1.5 MB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6qul.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6qul_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6qul_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 6qul_validation.xml.gz | 127.6 KB | 表示 | |
CIF形式データ | 6qul_validation.cif.gz | 216.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/qu/6qul ftp://data.pdbj.org/pub/pdb/validation_reports/qu/6qul | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-RNA鎖 , 3種, 3分子 1AB
#1: RNA鎖 | 分子量: 1223.818 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Escherichia coli (大腸菌) |
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#2: RNA鎖 | 分子量: 906514.125 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Escherichia coli (大腸菌) |
#3: RNA鎖 | 分子量: 38790.090 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Escherichia coli (大腸菌) / 参照: GenBank: 1476653947 |
+50S ribosomal protein ... , 28種, 28分子 CDEFGHKLMNOPQRSTUVWXYZabcdef
-非ポリマー , 5種, 386分子
#32: 化合物 | ChemComp-FME / | ||||||
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#33: 化合物 | ChemComp-MG / #34: 化合物 | ChemComp-A / | #35: 化合物 | ChemComp-JJH / | #36: 化合物 | ChemComp-ZN / | |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Structure of a bacterial 50S ribosomal subunit in complex with the novel quinoxolidinone antibiotic cadazolid タイプ: RIBOSOME / Entity ID: #1-#31 / 由来: NATURAL |
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分子量 | 単位: MEGADALTONS / 実験値: NO |
由来(天然) | 生物種: Escherichia coli (大腸菌) |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのタイプ: Quantifoil R2/2 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE-PROPANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 1.14 e/Å2 / 検出モード: INTEGRATING フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 59148 / 対称性のタイプ: POINT |