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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 | Bovine complex I in the presence of IM1761092, active class iii (Composite map) | |||||||||
![]() | Composite map of 3 focus refinements | |||||||||
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機能・相同性 | ![]() Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / Respiratory electron transport / gliogenesis / neural precursor cell proliferation / : / [2Fe-2S] cluster assembly ...Complex I biogenesis / Mitochondrial protein import / RHOG GTPase cycle / cellular response to oxygen levels / mitochondrial large ribosomal subunit binding / Respiratory electron transport / gliogenesis / neural precursor cell proliferation / : / [2Fe-2S] cluster assembly / oxygen sensor activity / ubiquinone-6 biosynthetic process / cellular respiration / Neutrophil degranulation / NADH dehydrogenase activity / mitochondrial ribosome / mitochondrial translation / Mitochondrial protein degradation / NADH:ubiquinone reductase (H+-translocating) / apoptotic mitochondrial changes / acyl binding / ubiquinone binding / acyl carrier activity / quinone binding / electron transport coupled proton transport / neurogenesis / ATP synthesis coupled electron transport / negative regulation of intrinsic apoptotic signaling pathway / ATP metabolic process / mitochondrial ATP synthesis coupled electron transport / mitochondrial respiratory chain complex I assembly / response to cAMP / respiratory electron transport chain / reactive oxygen species metabolic process / regulation of mitochondrial membrane potential / : / mitochondrial electron transport, NADH to ubiquinone / fatty acid binding / NADH dehydrogenase (ubiquinone) activity / apoptotic signaling pathway / electron transport chain / regulation of protein phosphorylation / brain development / mitochondrial membrane / aerobic respiration / mitochondrial intermembrane space / negative regulation of cell growth / 2 iron, 2 sulfur cluster binding / fatty acid biosynthetic process / positive regulation of fibroblast proliferation / NAD binding / FMN binding / 4 iron, 4 sulfur cluster binding / response to oxidative stress / oxidoreductase activity / mitochondrial inner membrane / structural constituent of ribosome / mitochondrial matrix / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / protein-containing complex binding / mitochondrion / nucleoplasm / metal ion binding / cytoplasm 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: 2.4 Å | |||||||||
![]() | Bridges HR / Blaza JN / Yin Z / Chung I / Hirst J | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. 著者: Hannah R Bridges / James N Blaza / Zhan Yin / Injae Chung / Michael N Pollak / Judy Hirst / ![]() ![]() 要旨: The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target ...The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides. | |||||||||
履歴 |
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 1021 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 62.5 KB 62.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 86.4 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 | ![]() 7r43MC ![]() 7qsdC ![]() 7r41C ![]() 7r42C ![]() 7r44C ![]() 7r45C ![]() 7r46C ![]() 7r47C ![]() 7r48C ![]() 7r4cC ![]() 7r4dC ![]() 7r4fC ![]() 7r4gC 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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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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注釈 | Composite map of 3 focus refinements | ||||||||||||||||||||||||||||||||||||
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: 0.731 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 : NADH Ubiquinone oxidoreductase (Complex I)
+超分子 #1: NADH Ubiquinone oxidoreductase (Complex I)
+分子 #1: NADH-ubiquinone oxidoreductase chain 3
+分子 #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+分子 #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+分子 #4: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+分子 #5: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+分子 #6: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+分子 #7: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+分子 #8: NADH-ubiquinone oxidoreductase chain 1
+分子 #9: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+分子 #10: NADH-ubiquinone oxidoreductase chain 6
+分子 #11: NADH-ubiquinone oxidoreductase chain 4L
+分子 #12: NADH-ubiquinone oxidoreductase chain 5
+分子 #13: NADH-ubiquinone oxidoreductase chain 4
+分子 #14: NADH-ubiquinone oxidoreductase chain 2
+分子 #15: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+分子 #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+分子 #17: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
+分子 #18: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+分子 #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+分子 #20: Acyl carrier protein, mitochondrial
+分子 #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+分子 #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+分子 #23: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+分子 #24: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11
+分子 #25: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+分子 #26: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+分子 #27: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+分子 #28: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+分子 #29: NADH dehydrogenase [ubiquinone] 1 subunit C2
+分子 #30: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+分子 #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+分子 #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+分子 #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+分子 #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+分子 #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+分子 #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+分子 #37: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+分子 #38: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+分子 #39: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+分子 #40: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+分子 #41: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+分子 #42: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+分子 #43: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+分子 #44: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+分子 #45: DODECYL-BETA-D-MALTOSIDE
+分子 #46: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #47: IRON/SULFUR CLUSTER
+分子 #48: FE2/S2 (INORGANIC) CLUSTER
+分子 #49: FLAVIN MONONUCLEOTIDE
+分子 #50: POTASSIUM ION
+分子 #51: 1,2-Distearoyl-sn-glycerophosphoethanolamine
+分子 #52: CARDIOLIPIN
+分子 #53: GUANOSINE-5'-TRIPHOSPHATE
+分子 #54: MAGNESIUM ION
+分子 #55: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+分子 #56: ZINC ION
+分子 #57: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
+分子 #58: MYRISTIC ACID
+分子 #59: water
-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
濃度 | 3 mg/mL | ||||||||||||
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緩衝液 | pH: 7.14 構成要素:
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グリッド | モデル: UltrAuFoil R0.6/1 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 90 sec. / 前処理 - 雰囲気: AIR 詳細: Grid also covalently modified by peg-thiol for 48 hours in a nitrogen atmosphere. | ||||||||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
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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 K3 BIOQUANTUM (6k x 4k) 検出モード: COUNTING / 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 | C2レンズ絞り径: 70.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 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): 1.0 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 | 解像度のタイプ: BY AUTHOR / 解像度: 2.4 Å / 解像度の算出法: OTHER / 詳細: D99 measure from PHENIX / 使用した粒子像数: 27326 |
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初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |