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Open data
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Basic information
Entry | Database: PDB / ID: 6y6x | |||||||||
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Title | Tetracenomycin X bound to the human ribosome | |||||||||
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![]() | ANTIBIOTIC / Translation inhibitor | |||||||||
Function / homology | ![]() eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / axial mesoderm development / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / 90S preribosome assembly / TORC2 complex binding / GAIT complex / middle ear morphogenesis ...eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / axial mesoderm development / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / 90S preribosome assembly / TORC2 complex binding / GAIT complex / middle ear morphogenesis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / alpha-beta T cell differentiation / regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of ubiquitin protein ligase activity / optic nerve development / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / lung morphogenesis / male meiosis I / Protein hydroxylation / macrophage chemotaxis / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / protein targeting / cellular response to interleukin-4 / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / cellular response to actinomycin D / cytosolic ribosome / rough endoplasmic reticulum / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / MDM2/MDM4 family protein binding / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / negative regulation of ubiquitin-dependent protein catabolic process / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / embryo implantation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
![]() | Buschauer, R. / Cheng, J. / Berninghausen, O. / Beckmann, R. / Wilson, D.N. | |||||||||
![]() | ![]() Title: Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel. Authors: Ilya A Osterman / Maximiliane Wieland / Tinashe P Maviza / Kseniya A Lashkevich / Dmitrii A Lukianov / Ekaterina S Komarova / Yuliya V Zakalyukina / Robert Buschauer / Dmitrii I Shiriaev / ...Authors: Ilya A Osterman / Maximiliane Wieland / Tinashe P Maviza / Kseniya A Lashkevich / Dmitrii A Lukianov / Ekaterina S Komarova / Yuliya V Zakalyukina / Robert Buschauer / Dmitrii I Shiriaev / Semen A Leyn / Jaime E Zlamal / Mikhail V Biryukov / Dmitry A Skvortsov / Vadim N Tashlitsky / Vladimir I Polshakov / Jingdong Cheng / Yury S Polikanov / Alexey A Bogdanov / Andrei L Osterman / Sergey E Dmitriev / Roland Beckmann / Olga A Dontsova / Daniel N Wilson / Petr V Sergiev / ![]() ![]() ![]() Abstract: The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct ...The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked. | |||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 3.1 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 219.2 KB | Display | |
Data in CIF | ![]() | 387.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 10709MC ![]() 6y69C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 3 types, 3 molecules L5L7L8
#1: RNA chain | Mass: 1639876.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#2: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#3: RNA chain | Mass: 50143.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+60S ribosomal protein ... , 42 types, 42 molecules LALBLCLDLELFLGLHLILJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLe...
-Protein , 1 types, 1 molecules Lm
#41: Protein | Mass: 6199.574 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Non-polymers , 3 types, 235 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/OCW.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/OCW.gif)
![](data/chem/img/ZN.gif)
#47: Chemical | ChemComp-MG / #48: Chemical | ChemComp-OCW / | #49: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Tetracenomycin bound to the human ribosome / Type: RIBOSOME / Entity ID: #1-#46 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 302737 / Symmetry type: POINT |