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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: 7ttw | ||||||||||||
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タイトル | 50S ribosomal subunit from Staphylococcus aureus containing double mutation in uL3 imparting linezolid resistance | ||||||||||||
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![]() | RIBOSOME / 50S subunit / antibiotic resistance / linezolid | ||||||||||||
機能・相同性 | ![]() large ribosomal subunit / large ribosomal subunit rRNA binding / 5S rRNA binding / transferase activity / cytosolic large ribosomal subunit / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome ...large ribosomal subunit / large ribosomal subunit rRNA binding / 5S rRNA binding / transferase activity / cytosolic large ribosomal subunit / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / cytoplasm 類似検索 - 分子機能 | ||||||||||||
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: 2.9 Å | ||||||||||||
![]() | Belousoff, M.J. / Piper, S. / Johnson, R. | ||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: A Structurally Characterized Evolutionary Escape Route from Treatment with the Antibiotic Linezolid. 著者: Laura Perlaza-Jiménez / Kher-Shing Tan / Sarah J Piper / Rachel M Johnson / Rebecca S Bamert / Christopher J Stubenrauch / Alexander Wright / David Lupton / Trevor Lithgow / Matthew J Belousoff / ![]() 要旨: Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen that presents great health concerns. Treatment requires the use of last-line antibiotics, such as members of the ...Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen that presents great health concerns. Treatment requires the use of last-line antibiotics, such as members of the oxazolidinone family, of which linezolid is the first member to see regular use in the clinic. Here, we report a short time scale selection experiment in which strains of MRSA were subjected to linezolid treatment. Clonal isolates which had evolved a linezolid-resistant phenotype were characterized by whole-genome sequencing. Linezolid-resistant mutants were identified which had accumulated mutations in the ribosomal protein uL3. Multiple clones which had two mutations in uL3 exhibited resistance to linezolid, 2-fold higher than the clinical breakpoint. Ribosomes from this strain were isolated and subjected to single-particle cryo-electron microscopic analysis and compared to the ribosomes from the parent strain. We found that the mutations in uL3 lead to a rearrangement of a loop that makes contact with Helix 90, propagating a structural change over 15 Å away. This distal change swings nucleotide U2504 into the binding site of the antibiotic, causing linezolid resistance. Antibiotic resistance poses a critical problem to human health and decreases the utility of these lifesaving drugs. Of particular concern is the "superbug" methicillin-resistant Staphylococcus aureus (MRSA), for which treatment of infection requires the use of last-line antibiotics, including linezolid. In this paper, we characterize the atomic rearrangements which the ribosome, the target of linezolid, undergoes during its evolutionary journey toward becoming drug resistant. Using cryo-electron microscopy, we describe a particular molecular mechanism which MRSA uses to become resistant to linezolid. | ||||||||||||
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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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ダウンロード
PDBx/mmCIF形式 | ![]() | 1.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 1.3 MB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.3 MB | 表示 | |
XML形式データ | ![]() | 121.3 KB | 表示 | |
CIF形式データ | ![]() | 209.4 KB | 表示 | |
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 | ![]() 26125MC ![]() 7ttuC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
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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
+50S ribosomal protein ... , 25種, 25分子 ABCDEFGHIJKLMNOPQRSVWXYZa
-RNA鎖 , 2種, 2分子 12
#26: RNA鎖 | 分子量: 946680.625 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 参照: GenBank: 1877770729 |
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#27: RNA鎖 | 分子量: 36998.973 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() |
-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: 50S ribosomal subunit from Staphylococcus aureus - double mutation in uL3 leading to linezolid resistance タイプ: RIBOSOME / Entity ID: all / 由来: NATURAL |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.4 |
試料 | 濃度: 0.3 mg/ml / 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
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 500 nm / C2レンズ絞り径: 50 µm |
撮影 | 電子線照射量: 47.5 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: FEI FALCON III (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 307600 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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