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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 3j79 | |||||||||
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| タイトル | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, large subunit | |||||||||
要素 |
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キーワード | RIBOSOME/INHIBITOR / emetine / RIBOSOME-INHIBITOR complex | |||||||||
| 機能・相同性 | 機能・相同性情報Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER ...Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / ER Quality Control Compartment (ERQC) / Iron uptake and transport / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Translation initiation complex formation / Formation of a pool of free 40S subunits / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / GTP hydrolysis and joining of the 60S ribosomal subunit / Negative regulators of DDX58/IFIH1 signaling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / PINK1-PRKN Mediated Mitophagy / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Aggrephagy / Orc1 removal from chromatin / CDK-mediated phosphorylation and removal of Cdc6 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / KEAP1-NFE2L2 pathway / UCH proteinases / Ub-specific processing proteases / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / MAPK6/MAPK4 signaling / ABC-family proteins mediated transport / AUF1 (hnRNP D0) binds and destabilizes mRNA / protein-RNA complex assembly / maturation of LSU-rRNA / cytosolic ribosome / ribosomal large subunit biogenesis / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / modification-dependent protein catabolic process / protein tag activity / large ribosomal subunit / ribosome biogenesis / 5S rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / ubiquitin-dependent protein catabolic process / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding / protein ubiquitination / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / RNA binding / zinc ion binding / nucleus / cytoplasm 類似検索 - 分子機能 | |||||||||
| 生物種 | ![]() | |||||||||
| 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: 3.2 Å | |||||||||
データ登録者 | Wong, W. / Bai, X.C. / Brown, A. / Fernandez, I.S. / Hanssen, E. / Condron, M. / Tan, Y.H. / Baum, J. / Scheres, S.H.W. | |||||||||
引用 | ジャーナル: Elife / 年: 2014タイトル: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. 著者: Wilson Wong / Xiao-chen Bai / Alan Brown / Israel S Fernandez / Eric Hanssen / Melanie Condron / Yan Hong Tan / Jake Baum / Sjors H W Scheres / ![]() 要旨: Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as ...Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3.2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery. | |||||||||
| 履歴 |
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構造の表示
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| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 3j79.cif.gz | 3 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb3j79.ent.gz | 表示 | PDB形式 | |
| PDBx/mmJSON形式 | 3j79.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
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/j7/3j79 ftp://data.pdbj.org/pub/pdb/validation_reports/j7/3j79 | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 2660MC ![]() 2661C ![]() 3j7aC ![]() 6okkC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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| 類似構造データ | |
| 電子顕微鏡画像生データ | EMPIAR-10028 (タイトル: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetineData size: 1.2 TB Data #1: Unaligned multi-frame micrographs [micrographs - multiframe] Data #2: Frame averaged micrographs [micrographs - single frame] Data #3: Processed shiny particles [picked particles - multiframe - processed]) |
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リンク
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集合体
| 登録構造単位 | ![]()
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要素
-RNA鎖 , 3種, 3分子 ABC
| #1: RNA鎖 | 分子量: 1216212.125 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() 株: 3D7 |
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| #2: RNA鎖 | 分子量: 38410.859 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() 株: 3D7 |
| #3: RNA鎖 | 分子量: 51206.461 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() 株: 3D7 |
+60S ribosomal protein ... , 42種, 42分子 DEFGHIJKLMNOPQRSTUVWXYZ0123456...
-非ポリマー , 2種, 168分子 


| #46: 化合物 | ChemComp-MG / #47: 化合物 | ChemComp-ZN / |
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-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 |
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試料調製
| 構成要素 | 名称: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine タイプ: RIBOSOME |
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| 分子量 | 値: 4.2 MDa / 実験値: NO |
| 緩衝液 | 名称: 20 mM HEPES, pH 7.4, 40 mM potassium acetate, 10 mM ammonium acetate, 10 mM magnesium acetate, 5 mM BME pH: 7.4 詳細: 20 mM HEPES, pH 7.4, 40 mM potassium acetate, 10 mM ammonium acetate, 10 mM magnesium acetate, 5 mM BME |
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 試料支持 | 詳細: holey carbon grids (Quantifoil R2/2) with home-made continuous carbon film, glow-discharged 30 seconds |
| 急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / Temp: 90 K / 湿度: 100 % 詳細: Blot 2.5 seconds before plunging into liquid ethane (FEI VITROBOT MARK IV). 手法: Blot 2.5 seconds before plunging |
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電子顕微鏡撮影
| 実験機器 | ![]() モデル: Tecnai Polara / 画像提供: FEI Company |
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| 顕微鏡 | モデル: FEI POLARA 300 / 日付: 2014年1月19日 |
| 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 / 倍率(公称値): 78000 X / 倍率(補正後): 104748 X / 最大 デフォーカス(公称値): 3800 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2 mm |
| 試料ホルダ | 資料ホルダタイプ: GATAN LIQUID NITROGEN / 温度: 85 K / 最高温度: 90 K / 最低温度: 80 K |
| 撮影 | 電子線照射量: 20 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 詳細: An in-house system was used to intercept videos from the detector at a rate of 17 frames/second (1 second exposures). |
| 画像スキャン | デジタル画像の数: 1083 |
| 放射波長 | 相対比: 1 |
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解析
| ソフトウェア | 名称: REFMAC / バージョン: 5.8.0077 2014/05/16 / 分類: 精密化 / Contact author: Garib N. Murshudov / Contact author email: garib[at]mrc-lmb.cam.ac.uk 解説: (un)restrained refinement or idealisation of macromolecular structures | ||||||||||||
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| EMソフトウェア |
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| CTF補正 | 詳細: Each particle | ||||||||||||
| 対称性 | 点対称性: C1 (非対称) | ||||||||||||
| 3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 105247 / ピクセルサイズ(公称値): 1.34 Å / ピクセルサイズ(実測値): 1.34 Å 詳細: A newly developed statistical movie processing approach was used to compensate for beam-induced movement. Refinement type: HALF-MAPS REFINED INDEPENDENTLY / 対称性のタイプ: POINT | ||||||||||||
| 精密化ステップ | サイクル: LAST
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