+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26822 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | A. baumannii 70S ribosome-Streptothricin-D complex | |||||||||
マップデータ | Acinetobacer baumannii ribosome 70S - SD complex with E-site tRNA | |||||||||
試料 |
| |||||||||
キーワード | Streptothricin / Nourseothricin / Antibiotic / Ribosome / Ribosome-RNA complex | |||||||||
機能・相同性 | 機能・相同性情報 ribosomal small subunit biogenesis / large ribosomal subunit / small ribosomal subunit rRNA binding / ribosomal small subunit assembly / small ribosomal subunit / transferase activity / large ribosomal subunit rRNA binding / 5S rRNA binding / cytosolic small ribosomal subunit / cytoplasmic translation ...ribosomal small subunit biogenesis / large ribosomal subunit / small ribosomal subunit rRNA binding / ribosomal small subunit assembly / small ribosomal subunit / transferase activity / large ribosomal subunit rRNA binding / 5S rRNA binding / cytosolic small ribosomal subunit / cytoplasmic translation / cytosolic large ribosomal subunit / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / RNA binding / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Acinetobacter baumannii AB0057 (バクテリア) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.21 Å | |||||||||
データ登録者 | Morgan CE / Yu EW | |||||||||
資金援助 | 米国, 1件
| |||||||||
引用 | ジャーナル: PLoS Biol / 年: 2023 タイトル: Streptothricin F is a bactericidal antibiotic effective against highly drug-resistant gram-negative bacteria that interacts with the 30S subunit of the 70S ribosome. 著者: Christopher E Morgan / Yoon-Suk Kang / Alex B Green / Kenneth P Smith / Matthew G Dowgiallo / Brandon C Miller / Lucius Chiaraviglio / Katherine A Truelson / Katelyn E Zulauf / Shade ...著者: Christopher E Morgan / Yoon-Suk Kang / Alex B Green / Kenneth P Smith / Matthew G Dowgiallo / Brandon C Miller / Lucius Chiaraviglio / Katherine A Truelson / Katelyn E Zulauf / Shade Rodriguez / Anthony D Kang / Roman Manetsch / Edward W Yu / James E Kirby / 要旨: The streptothricin natural product mixture (also known as nourseothricin) was discovered in the early 1940s, generating intense initial interest because of excellent gram-negative activity. Here, we ...The streptothricin natural product mixture (also known as nourseothricin) was discovered in the early 1940s, generating intense initial interest because of excellent gram-negative activity. Here, we establish the activity spectrum of nourseothricin and its main components, streptothricin F (S-F, 1 lysine) and streptothricin D (S-D, 3 lysines), purified to homogeneity, against highly drug-resistant, carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii. For CRE, the MIC50 and MIC90 for S-F and S-D were 2 and 4 μM, and 0.25 and 0.5 μM, respectively. S-F and nourseothricin showed rapid, bactericidal activity. S-F and S-D both showed approximately 40-fold greater selectivity for prokaryotic than eukaryotic ribosomes in in vitro translation assays. In vivo, delayed renal toxicity occurred at >10-fold higher doses of S-F compared with S-D. Substantial treatment effect of S-F in the murine thigh model was observed against the otherwise pandrug-resistant, NDM-1-expressing Klebsiella pneumoniae Nevada strain with minimal or no toxicity. Cryo-EM characterization of S-F bound to the A. baumannii 70S ribosome defines extensive hydrogen bonding of the S-F steptolidine moiety, as a guanine mimetic, to the 16S rRNA C1054 nucleobase (Escherichia coli numbering) in helix 34, and the carbamoylated gulosamine moiety of S-F with A1196, explaining the high-level resistance conferred by corresponding mutations at the residues identified in single rrn operon E. coli. Structural analysis suggests that S-F probes the A-decoding site, which potentially may account for its miscoding activity. Based on unique and promising activity, we suggest that the streptothricin scaffold deserves further preclinical exploration as a potential therapeutic for drug-resistant, gram-negative pathogens. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_26822.map.gz | 53.4 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-26822-v30.xml emd-26822.xml | 65 KB 65 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_26822.png | 122.6 KB | ||
Filedesc metadata | emd-26822.cif.gz | 13.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26822 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26822 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26822_validation.pdf.gz | 440.9 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_26822_full_validation.pdf.gz | 440.4 KB | 表示 | |
XML形式データ | emd_26822_validation.xml.gz | 8.9 KB | 表示 | |
CIF形式データ | emd_26822_validation.cif.gz | 10.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26822 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26822 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_26822.map.gz / 形式: CCP4 / 大きさ: 1000 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Acinetobacer baumannii ribosome 70S - SD complex with E-site tRNA | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.72 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-試料の構成要素
+全体 : SD-70S Ribosome Complex
+超分子 #1: SD-70S Ribosome Complex
+分子 #1: 50S ribosomal protein L33
+分子 #2: 50S ribosomal protein L34
+分子 #3: 50S ribosomal protein L35
+分子 #4: 50S ribosomal protein L36
+分子 #7: 50S ribosomal protein L2
+分子 #8: 50S ribosomal protein L3
+分子 #9: 50S ribosomal protein L4
+分子 #10: 50S ribosomal protein L5
+分子 #11: 50S ribosomal protein L6
+分子 #12: 50S ribosomal protein L9
+分子 #13: 50S ribosomal protein L13
+分子 #14: 50S ribosomal protein L14
+分子 #15: 50S ribosomal protein L15
+分子 #16: 50S ribosomal protein L16
+分子 #17: 50S ribosomal protein L17
+分子 #18: 50S ribosomal protein L18
+分子 #19: 50S ribosomal protein L19
+分子 #20: 50S ribosomal protein L20
+分子 #21: 50S ribosomal protein L21
+分子 #22: 50S ribosomal protein L22
+分子 #23: 50S ribosomal protein L23
+分子 #24: 50S ribosomal protein L24
+分子 #25: 50S ribosomal protein L25
+分子 #26: 50S ribosomal protein L27
+分子 #27: 50S ribosomal protein L28
+分子 #28: 50S ribosomal protein L29
+分子 #29: 50S ribosomal protein L30
+分子 #30: 50S ribosomal protein L32
+分子 #32: 30S ribosomal protein S2
+分子 #33: 30S ribosomal protein S3
+分子 #34: 30S ribosomal protein S4
+分子 #35: 30S ribosomal protein S5
+分子 #36: 30S ribosomal protein S6
+分子 #37: 30S ribosomal protein S7
+分子 #38: 30S ribosomal protein S8
+分子 #39: 30S ribosomal protein S9
+分子 #40: 30S ribosomal protein S10
+分子 #41: 30S ribosomal protein S11
+分子 #42: 30S ribosomal protein S12
+分子 #43: 30S ribosomal protein S13
+分子 #44: 30S ribosomal protein S14
+分子 #45: 30S ribosomal protein S15
+分子 #46: 30S ribosomal protein S16
+分子 #47: 30S ribosomal protein S17
+分子 #48: 30S ribosomal protein S18
+分子 #49: 30S ribosomal protein S19
+分子 #50: 30S ribosomal protein S20
+分子 #51: 30S ribosomal protein S21
+分子 #5: 23s ribosomal RNA
+分子 #6: 5s ribosomal RNA
+分子 #31: 16s Ribosomal RNA
+分子 #52: ZINC ION
+分子 #53: Streptothricin D
+分子 #54: MAGNESIUM ION
+分子 #55: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
---|---|
凍結 | 凍結剤: ETHANE |
-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: GATAN K3 (6k x 4k) / 平均電子線量: 36.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: INSILICO MODEL / In silico モデル: ab inito |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.21 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 420107 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |