+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6okk | ||||||
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タイトル | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit | ||||||
要素 |
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キーワード | ribosome/inhibitor / Protein synthesis (タンパク質生合成) / antimalarial drug / RIBOSOME (リボソーム) / ribosome-inhibitor complex | ||||||
機能・相同性 | 機能・相同性情報 RMTs methylate histone arginines / Protein methylation / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / 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 / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) ...RMTs methylate histone arginines / Protein methylation / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / 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 / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Ub-specific processing proteases / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / small-subunit processome / mRNA 5'-UTR binding / ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / ribosomal small subunit assembly / rRNA processing / cytosolic small ribosomal subunit / small ribosomal subunit / rRNA binding / リボソーム / structural constituent of ribosome / 翻訳 (生物学) / mRNA binding / 核小体 / ミトコンドリア / RNA binding / zinc ion binding / 細胞核 / 細胞質基質 類似検索 - 分子機能 | ||||||
生物種 | Plasmodium falciparum (マラリア病原虫) | ||||||
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: 3.3 Å | ||||||
データ登録者 | Wong, W. / Scheres, S.H.W. | ||||||
資金援助 | オーストラリア, 1件
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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
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 | 6okk.cif.gz | 1.7 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6okk.ent.gz | 1.4 MB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6okk.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/ok/6okk ftp://data.pdbj.org/pub/pdb/validation_reports/ok/6okk | HTTPS FTP |
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-関連構造データ
関連構造データ | 2660MC 2661C 3j79C 3j7aC 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 (文献) |
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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 emetine Data 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]) |
-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 , 2種, 2分子 Ag
#1: RNA鎖 | 分子量: 671337.500 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Plasmodium falciparum (isolate 3D7) (マラリア病原虫) 株: isolate 3D7 |
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#33: RNA鎖 | 分子量: 23774.059 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) Plasmodium falciparum (isolate 3D7) (マラリア病原虫) 株: isolate 3D7 |
+40S ribosomal protein ... , 31種, 31分子 BCDEFGHIJKLMNOPQRSTUVWXYZabcdef
-非ポリマー , 3種, 69分子
#34: 化合物 | ChemComp-MG / #35: 化合物 | ChemComp-34G / | #36: 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 |
-試料調製
構成要素 | 名称: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, small subunit タイプ: RIBOSOME / Entity ID: #1-#33 / 由来: NATURAL |
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由来(天然) | 生物種: Plasmodium falciparum 3D7 (マラリア病原虫) |
緩衝液 | pH: 7.2 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-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 |
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 FIELDBright-field microscopy |
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) |
-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: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 105247 / 対称性のタイプ: POINT | ||||||||||||
精密化 | 最高解像度: 3.3 Å |