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- PDB-9hl9: CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9hl9 | |||||||||
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Title | CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site tRNA AND mRNA : LM14Cs1H3 sKO STRAIN | |||||||||
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![]() | RIBOSOME / CRYO-EM / LEISHMANIA MAJOR / 80S / LM14Cs1H3 / snoRNA | |||||||||
Function / homology | ![]() ciliary transition zone / ciliary plasm / nuclear lumen / negative regulation of translational frameshifting / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / maturation of LSU-rRNA / translation regulator activity / rescue of stalled ribosome ...ciliary transition zone / ciliary plasm / nuclear lumen / negative regulation of translational frameshifting / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / maturation of LSU-rRNA / translation regulator activity / rescue of stalled ribosome / protein kinase C binding / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / kinase activity / ribosome biogenesis / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding / protein ubiquitination / structural constituent of ribosome / ribosome / translation / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / nucleolus / RNA binding / zinc ion binding / nucleoplasm / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
![]() | Rajan, K.S. / Yonath, A. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: -Alkoxy-Substituted Anisomycins with Potent Anti-Trypanosomiasis Activity and Expanded Modes of Action. Authors: Kajumee Bora Bhowal / Anh Minh Thao Nguyen / Ana Victoria Ibarra-Meneses / Andressa Brito Lira / K Shanmugha Rajan / Jesus D Castaño / Francis Beaudry / Anat Bashan / Christopher Fernandez- ...Authors: Kajumee Bora Bhowal / Anh Minh Thao Nguyen / Ana Victoria Ibarra-Meneses / Andressa Brito Lira / K Shanmugha Rajan / Jesus D Castaño / Francis Beaudry / Anat Bashan / Christopher Fernandez-Prada / Martin Olivier / Ada Yonath / William D Lubell / ![]() ![]() Abstract: Neglected tropical diseases caused by trypanosomatid parasites present a major public healthcare issue, partly due to emerging resistance. Attachment of ω-alkynyl chains characteristic of the lipid ...Neglected tropical diseases caused by trypanosomatid parasites present a major public healthcare issue, partly due to emerging resistance. Attachment of ω-alkynyl chains characteristic of the lipid tails of antiparasitic peptides to the -position of anisomycin gave ethers exhibiting potent activity, rivalling that of the parent ribosomal inhibitor, especially against resistant strains. Single-particle cryoelectron microscopy analysis revealed that -propargyl anisomycin binds to the highly conserved peptidyl transferase center of the ribosome similar to the parent inhibitor. Thermal proteomic profiling and gene ontology analysis demonstrated that -propargyl anisomycin exhibited a broader mode of action, including activity against glycosome-associated proteins. Alkynyl substituents improved antiparasitic activity against resistant strains, likely by enlarging the mode of action, offering a novel path toward therapy against trypanosomatid infections. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 4.9 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1.6 MB | Display | ![]() |
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Full document | ![]() | 1.9 MB | Display | |
Data in XML | ![]() | 349.6 KB | Display | |
Data in CIF | ![]() | 598.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 52247MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-RNA chain , 12 types, 12 molecules L1L2L3L4L5L6L7L8S3S4S5S1
#1: RNA chain | Mass: 577073.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
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#2: RNA chain | Mass: 492571.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#3: RNA chain | Mass: 69146.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: GenBank: 321438308 |
#4: RNA chain | Mass: 59466.293 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#5: RNA chain | Mass: 43503.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#6: RNA chain | Mass: 23336.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: GenBank: 321438308 |
#7: RNA chain | Mass: 54975.543 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: GenBank: 2105481105 |
#8: RNA chain | Mass: 39756.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#51: RNA chain | Mass: 25115.992 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#52: RNA chain | Mass: 24485.539 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: GenBank: 1851743410 |
#53: RNA chain | Mass: 4085.501 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
#88: RNA chain | Mass: 710683.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() |
+Putative 60S ... , 24 types, 24 molecules LALELFLHLILJLLLNLOLQLSLTLULVLWLZLaLcLeLhLiLlLnLp
-Putative ribosomal protein ... , 7 types, 7 molecules LBLCLXLgLkSMSS
#10: Protein | Mass: 47593.660 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q2Q6 |
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#11: Protein | Mass: 41096.855 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: E9ADW5 |
#32: Protein | Mass: 14608.168 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q1W6 |
#41: Protein | Mass: 16492.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QHL3 |
#45: Protein | Mass: 9479.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q8X0 |
#66: Protein | Mass: 13031.983 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q8G4 |
#72: Protein | Mass: 6696.929 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q817 |
-60S ribosomal protein ... , 9 types, 9 molecules LDLGLPLRLYLbLdLfLo
#12: Protein | Mass: 21694.502 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P48157 |
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#15: Protein | Mass: 29824.182 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QIP1 |
#24: Protein | Mass: 22071.080 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QG98 |
#26: Protein | Mass: 20852.338 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q5J4 |
#33: Protein | Mass: 15469.330 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q504 |
#36: Protein | Mass: 8001.308 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q178 |
#38: Protein | Mass: 11370.224 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: E9AEK1 |
#40: Protein | Mass: 15458.153 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QC11 |
#49: Protein | Mass: 10337.223 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QC01 |
-Putative 40S ribosomal protein ... , 14 types, 14 molecules LKSCSDSJSLSNSPSRSTSVSWSYScSd
#19: Protein | Mass: 19948.615 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QBJ1 |
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#56: Protein | Mass: 24511.762 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q4A0 |
#57: Protein | Mass: 22188.902 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QIM3 |
#63: Protein | Mass: 14719.258 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QGW3 |
#65: Protein | Mass: 16718.586 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q9A5 |
#67: Protein | Mass: 18681.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q1X7 |
#69: Protein | Mass: 15969.643 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QC89 |
#71: Protein | Mass: 17433.422 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q1Y3 |
#73: Protein | Mass: 17482.764 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q3M1 |
#75: Protein | Mass: 16551.529 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q806 |
#76: Protein | Mass: 17472.395 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QBV0 |
#78: Protein | Mass: 17035.592 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QH01 |
#82: Protein | Mass: 9819.463 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q140 |
#83: Protein | Mass: 9763.191 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q931 |
-Ribosomal protein ... , 3 types, 3 molecules LMLjSU
#21: Protein | Mass: 24497.971 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q6S3 |
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#44: Protein | Mass: 9862.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: E9AEH2 |
#74: Protein | Mass: 20023.457 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: A0A504XM54 |
-Ubiquitin-60S ribosomal protein ... , 2 types, 2 molecules LmSf
#47: Protein | Mass: 14711.425 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P69201 |
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#85: Protein | Mass: 17062.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QFK7 |
-Protein , 3 types, 3 molecules SASgSh
#54: Protein | Mass: 30033.955 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4FX73 |
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#86: Protein | Mass: 34441.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q7Y7 |
#87: Protein | Mass: 25229.275 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q5K7 |
-40S ribosomal protein ... , 14 types, 14 molecules SBSESFSGSHSISKSOSQSXSZSaSbSe
#55: Protein | Mass: 27536.629 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q0Q0 |
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#58: Protein | Mass: 30742.084 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QG31 |
#59: Protein | Mass: 28791.135 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QDL5 |
#60: Protein | Mass: 28370.227 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q9NE83 |
#61: Protein | Mass: 21336.623 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q868B1 |
#62: Protein | Mass: 23765.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: E9AC32 |
#64: Protein | Mass: 24984.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: P25204 |
#68: Protein | Mass: 15623.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q8H1 |
#70: Protein | Mass: 15627.837 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4QG97 |
#77: Protein | Mass: 18158.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: E9AEE8 |
#79: Protein | Mass: 15808.882 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q1D2 |
#80: Protein | Mass: 13071.399 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q9X4 |
#81: Protein | Mass: 12794.251 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q8L6 |
#84: Protein | Mass: 7394.894 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) ![]() References: UniProt: Q4Q7P0 |
-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 RIBOSOME WITH P/E-site tRNA AND mRNA / Type: RIBOSOME / Entity ID: #1-#50, #88, #51-#87 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.6 |
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: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 1.0018 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 138498 / Symmetry type: POINT | ||||||||||||||||||||||||
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