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Open data
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Basic information
Entry | Database: PDB / ID: 7mdz | ||||||
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Title | 80S rabbit ribosome stalled with benzamide-CHX | ||||||
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![]() | RIBOSOME / 80S mammalian ribosome / translation inhibitor | ||||||
Function / homology | ![]() ribosomal subunit / exit from mitosis / optic nerve development / laminin receptor activity / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / 90S preribosome / protein-RNA complex assembly ...ribosomal subunit / exit from mitosis / optic nerve development / laminin receptor activity / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / 90S preribosome / protein-RNA complex assembly / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / laminin binding / translation regulator activity / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / spindle / mRNA 5'-UTR binding / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / rhythmic process / positive regulation of canonical Wnt signaling pathway / regulation of translation / large ribosomal subunit / heparin binding / ribosome binding / virus receptor activity / ribosomal small subunit biogenesis / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / defense response to Gram-negative bacterium / killing of cells of another organism / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / cell differentiation / tRNA binding / mitochondrial inner membrane / postsynaptic density / rRNA binding / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / cell division / DNA repair / mRNA binding / apoptotic process / synapse / centrosome / dendrite / negative regulation of apoptotic process / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / Golgi apparatus / DNA binding / RNA binding / zinc ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | synthetic construct (others)![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Koga, Y. / Hoang, E.M. / Park, Y. / Keszei, A.F.A. / Murray, J. / Shao, S. / Liau, B.B. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation. Authors: Yumi Koga / Eileen M Hoang / Yongho Park / Alexander F A Keszei / Jason Murray / Sichen Shao / Brian B Liau / ![]() Abstract: Employed for over half a century to study protein synthesis, cycloheximide (CHX, ) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been ...Employed for over half a century to study protein synthesis, cycloheximide (CHX, ) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been applied to ribosome profiling, a method for mapping ribosome positions on mRNA genome-wide. Despite CHX's extensive use, CHX treatment often results in incomplete translation inhibition due to its rapid reversibility, prompting the need for improved reagents. Here, we report the concise synthesis of C13-amide-functionalized CHX derivatives with increased potencies toward protein synthesis inhibition. Cryogenic electron microscopy (cryo-EM) revealed that C13-aminobenzoyl CHX () occupies the same site as CHX, competing with the 3' end of E-site tRNA. We demonstrate that is superior to CHX for ribosome profiling experiments, enabling more effective capture of ribosome conformations through sustained stabilization of polysomes. Our studies identify powerful chemical reagents to study protein synthesis and reveal the molecular basis of their enhanced potency. | ||||||
History |
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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 | ![]() | 4.6 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23785MC 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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1 |
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Components
-Ribosomal protein ... , 7 types, 7 molecules ANQRVjDD
#1: Protein | Mass: 28088.863 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#13: Protein | Mass: 24207.285 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#16: Protein | Mass: 21699.688 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#17: Protein | Mass: 23535.281 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#21: Protein | Mass: 14892.505 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#35: Protein | Mass: 11111.032 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#46: Protein | Mass: 26715.344 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() References: UniProt: G1TNM3, DNA-(apurinic or apyrimidinic site) lyase |
+Protein , 45 types, 45 molecules BDOPTUXYcdefhlmoprBBCCFFGGHHIIJJKKLLMMNNOO...
-60S ribosomal protein ... , 18 types, 18 molecules CEFGHIJLMSWZabgikn
#3: Protein | Mass: 47727.559 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#5: Protein | Mass: 33028.336 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#6: Protein | Mass: 29201.836 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#7: Protein | Mass: 36221.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#8: Protein | Mass: 21871.418 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#9: Protein | Mass: 24643.057 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#10: Protein | Mass: 20288.465 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#11: Protein | Mass: 24331.723 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#12: Protein | Mass: 23870.549 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#18: Protein | Mass: 20827.561 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#22: Protein | Mass: 17825.111 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#25: Protein | Mass: 15835.831 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#26: Protein | Mass: 16620.561 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#27: Protein | Mass: 26708.707 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#32: Protein | Mass: 13196.894 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#34: Protein | Mass: 12263.834 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#36: Protein | Mass: 8238.948 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#39: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-40S ribosomal protein ... , 5 types, 5 molecules AAEEVVYYaa
#43: Protein | Mass: 32958.016 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#47: Protein | Mass: 29654.869 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#64: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#67: Protein | Mass: 15107.924 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#69: Protein | Mass: 13047.532 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-RNA chain , 6 types, 6 molecules 578296
#76: RNA chain | Mass: 1167622.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#77: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#78: RNA chain | Mass: 50143.648 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#79: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#80: RNA chain | Mass: 602777.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#81: RNA chain | Mass: 3139.876 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() |
-Non-polymers , 3 types, 286 molecules 




#82: Chemical | ChemComp-MG / #83: Chemical | ChemComp-ZN / #84: Chemical | ChemComp-Z2V / | |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: 80S rabbit ribosome stalled with benzamide-CHX / Type: RIBOSOME / Entity ID: #1-#81 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 4 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil |
Vitrification | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 3 sec blot |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 47 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software | Name: RELION / Category: image acquisition |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 34783 / Symmetry type: POINT |
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |
Atomic model building | PDB-ID: 6SGC Accession code: 6SGC / Source name: PDB / Type: experimental model |