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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7lo8 | |||||||||||||||||||||||||||
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タイトル | NorA in complex with Fab36 | |||||||||||||||||||||||||||
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![]() | TRANSPORT PROTEIN / efflux pump / antibiotic resistance | |||||||||||||||||||||||||||
機能・相同性 | ![]() | |||||||||||||||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.16 Å | |||||||||||||||||||||||||||
![]() | Brawley, D.N. / Sauer, D.B. / Song, J.M. / Koide, A. / Koide, S. / Traaseth, N.J. / Wang, D.N. | |||||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus. 著者: Douglas N Brawley / David B Sauer / Jianping Li / Xuhui Zheng / Akiko Koide / Ganesh S Jedhe / Tiffany Suwatthee / Jinmei Song / Zheng Liu / Paramjit S Arora / Shohei Koide / Victor J Torres ...著者: Douglas N Brawley / David B Sauer / Jianping Li / Xuhui Zheng / Akiko Koide / Ganesh S Jedhe / Tiffany Suwatthee / Jinmei Song / Zheng Liu / Paramjit S Arora / Shohei Koide / Victor J Torres / Da-Neng Wang / Nathaniel J Traaseth / ![]() ![]() ![]() 要旨: Membrane protein efflux pumps confer antibiotic resistance by extruding structurally distinct compounds and lowering their intracellular concentration. Yet, there are no clinically approved drugs to ...Membrane protein efflux pumps confer antibiotic resistance by extruding structurally distinct compounds and lowering their intracellular concentration. Yet, there are no clinically approved drugs to inhibit efflux pumps, which would potentiate the efficacy of existing antibiotics rendered ineffective by drug efflux. Here we identified synthetic antigen-binding fragments (Fabs) that inhibit the quinolone transporter NorA from methicillin-resistant Staphylococcus aureus (MRSA). Structures of two NorA-Fab complexes determined using cryo-electron microscopy reveal a Fab loop deeply inserted in the substrate-binding pocket of NorA. An arginine residue on this loop interacts with two neighboring aspartate and glutamate residues essential for NorA-mediated antibiotic resistance in MRSA. Peptide mimics of the Fab loop inhibit NorA with submicromolar potency and ablate MRSA growth in combination with the antibiotic norfloxacin. These findings establish a class of peptide inhibitors that block antibiotic efflux in MRSA by targeting indispensable residues in NorA without the need for membrane permeability. | |||||||||||||||||||||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 154.9 KB | 表示 | ![]() |
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PDB形式 | ![]() | 123.2 KB | 表示 | ![]() |
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その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 23464MC ![]() 7lo7C M: このデータのモデリングに利用したマップデータ 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
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 42353.238 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: norA, tetA, tetA_2, BTN44_09105, DD547_00670, DQV53_04080, EP54_04170, EQ90_03440, FA040_06730, G0V24_03995, G0X12_10865, G0Z18_04370, G6Y10_04720, GO746_14090, GO803_07545, GO805_01365, ...遺伝子: norA, tetA, tetA_2, BTN44_09105, DD547_00670, DQV53_04080, EP54_04170, EQ90_03440, FA040_06730, G0V24_03995, G0X12_10865, G0Z18_04370, G6Y10_04720, GO746_14090, GO803_07545, GO805_01365, GO821_08105, GO894_15090, GO942_03500, HMPREF2819_04810, HMPREF3211_00604, NCTC10654_00801, NCTC10702_01167, NCTC10988_00893, NCTC9944_00776, RK64_04180, SAMEA1029528_00668, SAMEA1029547_01044, SAMEA1029553_00751, SAMEA1964876_01266, SAMEA1965205_01031, SAMEA1966505_00819, SAMEA1969349_01052, SAMEA1969845_01011, SAMEA1971706_01410, SAMEA1972827_00559, SAMEA2076212_00937, SAMEA2076218_00794, SAMEA2076220_00416, SAMEA2076226_00094, SAMEA2076463_00402, SAMEA2076464_00402, SAMEA2076470_00989, SAMEA2076472_00906, SAMEA2076478_00948, SAMEA2076480_00403, SAMEA2076481_00754, SAMEA2076743_00851, SAMEA2076745_01198, SAMEA2076746_00709, SAMEA2076747_00402, SAMEA2076749_01092, SAMEA2076751_00767, SAMEA2076752_01693, SAMEA2076755_01477, SAMEA2076756_01730, SAMEA2076758_01750, SAMEA2076759_01476, SAMEA2076761_01673, SAMEA2076762_01568, SAMEA2076763_01005, SAMEA2076764_01192, SAMEA2076765_00813, SAMEA2077023_01193, SAMEA2077025_00963, SAMEA2077027_00992, SAMEA2077029_00946, SAMEA2077031_00749, SAMEA2077034_01532, SAMEA2077035_00441, SAMEA2077039_00933, SAMEA2077040_00402, SAMEA2077041_01231, SAMEA2077044_01041, SAMEA2077045_01087, SAMEA2077046_01075, SAMEA2077293_01085, SAMEA2077294_01001, SAMEA2077295_01088, SAMEA2077297_00893, SAMEA2077300_01388, SAMEA2077301_01079, SAMEA2077302_01294, SAMEA2077303_01165, SAMEA2077307_01110, SAMEA2077832_01179, SAMEA2078252_00991, SAMEA2078256_00442, SAMEA2078307_00767, SAMEA2078308_00437, SAMEA2078553_00705, SAMEA2078558_00440, SAMEA2078560_00441, SAMEA2078569_01033, SAMEA2078570_00726, SAMEA2078572_00766, SAMEA2078824_00440, SAMEA2078837_00724, SAMEA2079048_01019, SAMEA2079051_00890, SAMEA2079277_00570, SAMEA2079291_00132, SAMEA2079503_00716, SAMEA2079507_01569, SAMEA2079512_00399, SAMEA2079517_00401, SAMEA2079724_00193, SAMEA2079727_00743, SAMEA2079728_01205, SAMEA2079732_00659, SAMEA2079742_00929, SAMEA2079946_00528, SAMEA2079949_00512, SAMEA2079951_00193, SAMEA2079952_00660, SAMEA2079957_00881, SAMEA2079958_00559, SAMEA2079960_00657, SAMEA2079961_00193, SAMEA2079968_00614, SAMEA2080329_00094, SAMEA2080330_00193, SAMEA2080334_00929, SAMEA2080433_00981, SAMEA2080812_00715, SAMEA2080898_00727, SAMEA2080900_00662, SAMEA2080904_00710, SAMEA2080913_00729, SAMEA2081043_01808, SAMEA2081053_01006, SAMEA2081054_00654, SAMEA2081055_00993, SAMEA2081060_00553, SAMEA2081211_01079, SAMEA2081213_00399, SAMEA2081218_00473, SAMEA2081341_00094, SAMEA2081342_00612, SAMEA2081349_00936, SAMEA2081359_00094, SAMEA2081362_00860, SAMEA2081468_00628, SAMEA2081474_00441, SAMEA2081475_00651, SAMEA2081476_01465, SAMEA2081479_01707, SAMEA2081480_01854, SAMEA2081560_01571, SAMEA2081561_01009, SAMEA2081564_00963, SAMEA2081567_00976, SAMEA2081568_01004, SAMEA2081569_00706, SAMEA2081570_00962, SAMEA2081571_00711, SAMEA2081572_00947, SAMEA2081573_00955, SAMEA2081575_01082, SAMEA2081577_00891, SAMEA2081578_00766, SAMEA2081579_01168, SAMEA2081581_01073, SAMEA2081582_01166, SAMEA2081673_00935, SAMEA2081674_00934, SAMEA958766_00618, SAMEA958770_01028, SAMEA958772_00649, SAMEA958778_01022, SAMEA958779_00094, SAMEA958785_00651, SAMEA958793_00683, SAMEA958798_00328, SAMEA958804_01063, SAMEA958810_00661, SAMEA958836_01276, SAMEA958838_00069, SAMEA958845_00683, SAMEA958846_00694, SAMEA958848_01177, SAMEA958855_00578, SAMEA958858_00913, SAMEA958870_01324, SAMEA958898_01209, SAMEA958906_00445, SAMEA958925_01036, SAMEA958951_01582, SAMEA958953_00694, SAMEA958961_00691, SAMEA958979_00607, SAMEA958987_00401, SAMEA958995_00511 プラスミド: pET28a / 詳細 (発現宿主): C-term 10 His tag / Cell (発現宿主): E. coli / 発現宿主: ![]() ![]() |
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#2: 抗体 | 分子量: 28044.465 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#3: 抗体 | 分子量: 25794.859 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: NorA:Fab36 complex / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 55.54 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.16 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 311335 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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