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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 | |||||||||
![]() | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 (unsharpened) | |||||||||
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![]() | ATP synthase / mycobacterial / inhibitor / tuberculosis / antibiotic / HYDROLASE / TRANSLOCASE-INHIBITOR complex | |||||||||
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) / 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 / ADP binding / hydrolase activity ...proton motive force-driven plasma membrane ATP synthesis / photosynthetic electron transport in photosystem I / proton-transporting ATP synthase complex, coupling factor F(o) / 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 / ADP binding / hydrolase activity / lipid binding / ATP hydrolysis activity / ATP binding / plasma membrane 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: 2.6 Å | |||||||||
![]() | Courbon GM / Rubinstein JL | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines. 著者: Gautier M Courbon / Paul R Palme / Lea Mann / Adrian Richter / Peter Imming / John L Rubinstein / ![]() ![]() 要旨: Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase ...Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase inhibitor, is an important medication for treatment of drug-resistant tuberculosis but suffers from off-target effects and is susceptible to resistance mutations. Consequently, both new and improved mycobacterial ATP synthase inhibitors are needed. We used electron cryomicroscopy and biochemical assays to study the interaction of Mycobacterium smegmatis ATP synthase with the second generation diarylquinoline TBAJ-876 and the squaramide inhibitor SQ31f. The aryl groups of TBAJ-876 improve binding compared with BDQ, while SQ31f, which blocks ATP synthesis ~10 times more potently than ATP hydrolysis, binds a previously unknown site in the enzyme's proton-conducting channel. Remarkably, BDQ, TBAJ-876, and SQ31f all induce similar conformational changes in ATP synthase, suggesting that the resulting conformation is particularly suited for drug binding. Further, high concentrations of the diarylquinolines uncouple the transmembrane proton motive force while for SQ31f they do not, which may explain why high concentrations of diarylquinolines, but not SQ31f, have been reported to kill mycobacteria. | |||||||||
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FSC (解像度算出) | ![]() | 11.9 KB | 表示 | ![]() |
画像 | ![]() | 74.9 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
その他 | ![]() ![]() ![]() | 58.1 MB 116 MB 116 MB | ||
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 | ![]() 8g0eMC ![]() 8g07C ![]() 8g08C ![]() 8g09C ![]() 8g0aC ![]() 8g0bC ![]() 8g0cC ![]() 8g0dC 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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注釈 | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 (unsharpened) | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.03 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
-追加マップ: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase...
ファイル | emd_29655_additional_1.map | ||||||||||||
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注釈 | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 (locally sharpened) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase...
ファイル | emd_29655_half_map_1.map | ||||||||||||
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注釈 | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 (Half A) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase...
ファイル | emd_29655_half_map_2.map | ||||||||||||
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注釈 | Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3 (Half B) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
+全体 : TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3
+超分子 #1: TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 3
+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 b
+分子 #6: ATP synthase subunit b-delta
+分子 #7: ATP synthase subunit c
+分子 #8: ATP synthase subunit a
+分子 #9: ADENOSINE-5'-TRIPHOSPHATE
+分子 #10: MAGNESIUM ION
+分子 #11: PHOSPHATE ION
+分子 #12: (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxypyridi...
-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: 44.0 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): 2.1 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |