- EMDB-14121: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex ... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-14121
タイトル
Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A.
マップデータ
Masked post processed map
試料
複合体: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A.
RNA: x 2種
タンパク質・ペプチド: x 27種
リガンド: x 3種
キーワード
Ribosome / Antibiotic / Myxovalargin A / MyxA
機能・相同性
機能・相同性情報
transcriptional attenuation / positive regulation of ribosome biogenesis / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / assembly of large subunit precursor of preribosome ...transcriptional attenuation / positive regulation of ribosome biogenesis / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / negative regulation of cytoplasmic translation / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / mRNA regulatory element binding translation repressor activity / assembly of large subunit precursor of preribosome / ribosome assembly / cytosolic ribosome assembly / response to reactive oxygen species / regulation of cell growth / DNA-templated transcription termination / response to radiation / mRNA 5'-UTR binding / large ribosomal subunit / ribosome binding / transferase activity / 5S rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / translation / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / cytosol / cytoplasm 類似検索 - 分子機能
Ribosomal protein L25, short-form / : / Ribosomal protein L16 signature 1. / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / : ...Ribosomal protein L25, short-form / : / Ribosomal protein L16 signature 1. / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / : / Ribosomal protein L17 signature. / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L36 signature. / Ribosomal protein L28/L24 superfamily / Ribosomal protein L32p, bacterial type / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / : / Ribosomal protein L28 / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L18, bacterial-type / : / Ribosomal protein L6, bacterial-type / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein L20 signature. / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L14P, bacterial-type / Ribosomal protein L34, conserved site / Ribosomal protein L34 signature. / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L35 / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal L28 family / Ribosomal protein L33 superfamily / Ribosomal protein L16 / Ribosomal protein L28/L24 / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / Ribosomal protein L30, bacterial-type / : / L28p-like / Ribosomal protein L27 / Ribosomal L27 protein / Ribosomal protein L20 / Ribosomal L32p protein family / Ribosomal protein L19 / Ribosomal protein L19 / Ribosomal protein L20 / Ribosomal protein L20, C-terminal / Ribosomal protein L19 superfamily / Ribosomal protein L21 / Ribosomal protein L17 / Ribosomal protein L32p / Ribosomal protein L17 superfamily / Ribosomal protein L17 / Ribosomal proteins 50S L24/mitochondrial 39S L24 / Ribosomal protein L21-like / L21-like superfamily / Ribosomal prokaryotic L21 protein / Ribosomal protein L24 / Ribosomal protein L34 / Ribosomal protein L34 / Ribosomal protein L13, bacterial-type / Ribosomal protein L3, bacterial/organelle-type / Ribosomal protein L15, bacterial-type / 50S ribosomal protein uL4 / Ribosomal protein L23/L25, conserved site / Ribosomal protein L23 signature. / Ribosomal protein L30, conserved site / Ribosomal protein L30 signature. / Ribosomal protein L2 signature. / Ribosomal protein L29, conserved site / Ribosomal protein L29 signature. / Ribosomal protein L2, conserved site / : / Ribosomal protein L15, conserved site / Ribosomal protein L15 signature. / Ribosomal protein L10e/L16 / Ribosomal protein L10e/L16 superfamily / Ribosomal protein L16p/L10e / Ribosomal protein L6, alpha-beta domain / Ribosomal protein L6 / Ribosomal protein L6 / Ribosomal protein L6, alpha-beta domain superfamily / Ribosomal protein L13 signature. / Ribosomal protein L2, domain 3 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL20 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL32 / Large ribosomal subunit protein bL33 / Large ribosomal subunit protein bL34 / Large ribosomal subunit protein bL35 ...Large ribosomal subunit protein uL15 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL20 / Large ribosomal subunit protein bL27 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL32 / Large ribosomal subunit protein bL33 / Large ribosomal subunit protein bL34 / Large ribosomal subunit protein bL35 / Large ribosomal subunit protein bL36A / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein bL21 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein bL25 類似検索 - 構成要素
ジャーナル: J Am Chem Soc / 年: 2023 タイトル: The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition. 著者: Timm O Koller / Ullrich Scheid / Teresa Kösel / Jennifer Herrmann / Daniel Krug / Helena I M Boshoff / Bertrand Beckert / Joanna C Evans / Jan Schlemmer / Becky Sloan / Danielle M Weiner / ...著者: Timm O Koller / Ullrich Scheid / Teresa Kösel / Jennifer Herrmann / Daniel Krug / Helena I M Boshoff / Bertrand Beckert / Joanna C Evans / Jan Schlemmer / Becky Sloan / Danielle M Weiner / Laura E Via / Atica Moosa / Thomas R Ioerger / Michael Graf / Boris Zinshteyn / Maha Abdelshahid / Fabian Nguyen / Stefan Arenz / Franziska Gille / Maik Siebke / Tim Seedorf / Oliver Plettenburg / Rachel Green / Anna-Luisa Warnke / Joachim Ullrich / Ralf Warrass / Clifton E Barry / Digby F Warner / Valerie Mizrahi / Andreas Kirschning / Daniel N Wilson / Rolf Müller / 要旨: Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum ...Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent.
全体 : Cryo-EM structure of the E.coli 50S ribosomal subunit in complex ...
全体
名称: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A.
要素
複合体: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A.
RNA: 23S ribosomal RNA
RNA: 5S ribosomal RNA
タンパク質・ペプチド: 50S ribosomal protein L2
タンパク質・ペプチド: 50S ribosomal protein L3
タンパク質・ペプチド: 50S ribosomal protein L4
タンパク質・ペプチド: 50S ribosomal protein L6
タンパク質・ペプチド: 50S ribosomal protein L13
タンパク質・ペプチド: 50S ribosomal protein L14
タンパク質・ペプチド: 50S ribosomal protein L15
タンパク質・ペプチド: 50S ribosomal protein L16
タンパク質・ペプチド: 50S ribosomal protein L17
タンパク質・ペプチド: 50S ribosomal protein L18
タンパク質・ペプチド: 50S ribosomal protein L19
タンパク質・ペプチド: 50S ribosomal protein L20
タンパク質・ペプチド: 50S ribosomal protein L21
タンパク質・ペプチド: 50S ribosomal protein L22
タンパク質・ペプチド: 50S ribosomal protein L23
タンパク質・ペプチド: 50S ribosomal protein L24
タンパク質・ペプチド: 50S ribosomal protein L25
タンパク質・ペプチド: 50S ribosomal protein L27
タンパク質・ペプチド: 50S ribosomal protein L28
タンパク質・ペプチド: 50S ribosomal protein L29
タンパク質・ペプチド: 50S ribosomal protein L30
タンパク質・ペプチド: 50S ribosomal protein L32
タンパク質・ペプチド: 50S ribosomal protein L33
タンパク質・ペプチド: 50S ribosomal protein L34
タンパク質・ペプチド: 50S ribosomal protein L35
タンパク質・ペプチド: 50S ribosomal protein L36
タンパク質・ペプチド: Myxovalargin A
リガンド: MAGNESIUM ION
リガンド: ZINC ION
リガンド: water
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超分子 #1: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex ...
超分子
名称: Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#29