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データを開く
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of the Mycobacterium tuberculosis cytochrome bcc:aa3 supercomplex and a novel inhibitor targeting subunit cytochrome cI | |||||||||
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![]() | Cytochrome bcc:aa3 oxidase / Mycobacterium tuberculosis / OXIDOREDUCTASE | |||||||||
機能・相同性 | ![]() oxidoreduction-driven active transmembrane transporter activity / aerobic electron transport chain / cytochrome-c oxidase / oxidative phosphorylation / quinol-cytochrome-c reductase / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / electron transport coupled proton transport / : ...oxidoreduction-driven active transmembrane transporter activity / aerobic electron transport chain / cytochrome-c oxidase / oxidative phosphorylation / quinol-cytochrome-c reductase / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / ubiquinol-cytochrome-c reductase activity / cytochrome-c oxidase activity / electron transport coupled proton transport / : / monooxygenase activity / respiratory electron transport chain / aerobic respiration / 2 iron, 2 sulfur cluster binding / electron transfer activity / iron ion binding / heme binding / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 電子線トモグラフィー法 / クライオ電子顕微鏡法 | |||||||||
![]() | Mathiyazakan V / Gruber G | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-Electron Microscopy Structure of the s Cytochrome : Supercomplex and a Novel Inhibitor Targeting Subunit Cytochrome I. 著者: Vikneswaran Mathiyazakan / Chui-Fann Wong / Amaravadhi Harikishore / Kevin Pethe / Gerhard Grüber / ![]() 要旨: The mycobacterial cytochrome complex deserves the name "supercomplex" since it combines three cytochrome oxidases-cytochrome , cytochrome , and cytochrome -into one supramolecular machine and ...The mycobacterial cytochrome complex deserves the name "supercomplex" since it combines three cytochrome oxidases-cytochrome , cytochrome , and cytochrome -into one supramolecular machine and performs electron transfer for the reduction of oxygen to water and proton transport to generate the proton motive force for ATP synthesis. Thus, the complex represents a valid drug target for Mycobacterium tuberculosis infections. The production and purification of an entire M. tuberculosis cytochrome are fundamental for biochemical and structural characterization of this supercomplex, paving the way for new inhibitor targets and molecules. Here, we produced and purified the entire and active M. tuberculosis cyt- oxidase, as demonstrated by the different heme spectra and an oxygen consumption assay. The resolved M. tuberculosis cyt- cryo-electron microscopy structure reveals a dimer with its functional domains involved in electron, proton, oxygen transfer, and oxygen reduction. The structure shows the two cytochrome III head domains of the dimer, the counterpart of the soluble mitochondrial cytochrome , in a so-called "closed state," in which electrons are translocated from the to the domain. The structural and mechanistic insights provided the basis for a virtual screening campaign that identified a potent M. tuberculosis cyt- inhibitor, cyt1. cyt1 targets the mycobacterium-specific α3-helix of cytochrome I and interferes with oxygen consumption by interrupting electron translocation via the III head. The successful identification of a new cyt- inhibitor demonstrates the potential of a structure-mechanism-based approach for novel compound development. | |||||||||
履歴 |
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構造の表示
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マップデータ | ![]() | 450.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.7 KB 21.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 84.9 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 | ![]() 8hcrMC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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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: 1.06 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 : Cytochrome bcc:aa3 supercomplex
+超分子 #1: Cytochrome bcc:aa3 supercomplex
+分子 #1: Cytochrome bc1 complex Rieske iron-sulfur subunit
+分子 #2: Cytochrome bc1 complex cytochrome b subunit
+分子 #3: Cytochrome bc1 complex cytochrome c subunit
+分子 #4: CYTOCHROME AA3 SUBUNIT CtaC
+分子 #5: Probable cytochrome c oxidase subunit 1
+分子 #6: Probable cytochrome c oxidase subunit 3
+分子 #7: Cytochrome c oxidase polypeptide 4
+分子 #8: CYTOCHROME AA3 SUBUNIT CtaJ
+分子 #9: DUF5130 domain-containing protein
+分子 #10: FE2/S2 (INORGANIC) CLUSTER
+分子 #11: PROTOPORPHYRIN IX CONTAINING FE
+分子 #12: HEME C
+分子 #13: HEME-A
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 電子線トモグラフィー法 |
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 |
切片作成 | その他: NO SECTIONING |
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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: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 40.0 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): 2.0 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 |
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画像解析
最終 再構成 | 使用した粒子像数: 100 |
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