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基本情報
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タイトル | Cryo-EM structure of Mycobacterium tuberculosis ATP synthase in the apo-form | ||||||||||||
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![]() | ATP synthase / Mycobacterium tuberculosis / cryo-EM / MEMBRANE PROTEIN | ||||||||||||
機能・相同性 | ![]() proton motive force-driven plasma membrane ATP synthesis / photosynthetic electron transport in photosystem I / proton-transporting ATP synthase complex, coupling factor F(o) / proton motive force-driven ATP synthesis / photosynthetic electron transport in photosystem II / proton-transporting ATP synthase complex, catalytic core F(1) / H+-transporting two-sector ATPase / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / peptidoglycan-based cell wall ...proton motive force-driven plasma membrane ATP synthesis / photosynthetic electron transport in photosystem I / proton-transporting ATP synthase complex, coupling factor F(o) / proton motive force-driven ATP synthesis / photosynthetic electron transport in photosystem II / proton-transporting ATP synthase complex, catalytic core F(1) / H+-transporting two-sector ATPase / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / peptidoglycan-based cell wall / ADP binding / hydrolase activity / lipid binding / ATP hydrolysis activity / extracellular region / ATP binding / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.8 Å | ||||||||||||
![]() | Zhang Y / Lai Y / Liu F / Rao Z / Gong H | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587. 著者: Yuying Zhang / Yuezheng Lai / Shan Zhou / Ting Ran / Yue Zhang / Ziqing Zhao / Ziyan Feng / Long Yu / Jinxu Xu / Kun Shi / Jianyun Wang / Yu Pang / Liang Li / Hongming Chen / Luke W Guddat / ...著者: Yuying Zhang / Yuezheng Lai / Shan Zhou / Ting Ran / Yue Zhang / Ziqing Zhao / Ziyan Feng / Long Yu / Jinxu Xu / Kun Shi / Jianyun Wang / Yu Pang / Liang Li / Hongming Chen / Luke W Guddat / Yan Gao / Fengjiang Liu / Zihe Rao / Hongri Gong / ![]() ![]() 要旨: Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. ...Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. However, BDQ also inhibits human ATP synthase. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs. | ||||||||||||
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マップデータ | ![]() | 467.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 22.1 KB 22.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 41.5 KB | ||
Filedesc metadata | ![]() | 7.5 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8j0tMC ![]() 8j0sC ![]() 8j57C ![]() 8j58C ![]() 8jr0C ![]() 8jr1C ![]() 8khfC ![]() 8ki3C ![]() 37029 C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.73 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Mycobacterium tuberculosis ATP synthase
+超分子 #1: Mycobacterium tuberculosis ATP synthase
+分子 #1: ATP synthase subunit alpha
+分子 #2: ATP synthase subunit beta
+分子 #3: ATP synthase gamma chain
+分子 #4: ATP synthase epsilon chain
+分子 #5: ATP synthase subunit c
+分子 #6: ATP synthase subunit a
+分子 #7: ATP synthase subunit b
+分子 #8: Multifunctional fusion protein
+分子 #9: ADENOSINE-5'-TRIPHOSPHATE
+分子 #10: MAGNESIUM ION
+分子 #11: ADENOSINE-5'-DIPHOSPHATE
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.4 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: OTHER / 詳細: AlphaFold |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 66593 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |