[English] 日本語
Yorodumi- PDB-9hl9: CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site ... -
+
Open data
-
Basic information
| Entry | Database: PDB / ID: 9hl9 | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site tRNA AND mRNA : LM14Cs1H3 sKO STRAIN | ||||||||||||||||||||||||
Components |
| ||||||||||||||||||||||||
Keywords | RIBOSOME / CRYO-EM / LEISHMANIA MAJOR / 80S / LM14Cs1H3 / snoRNA | ||||||||||||||||||||||||
| Function / homology | Function and homology informationciliary 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) / protein-RNA complex assembly / maturation of 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) / translation regulator activity / rescue of stalled cytosolic 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) / protein-RNA complex assembly / maturation of 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) / translation regulator activity / rescue of stalled cytosolic ribosome / protein kinase C binding / ribosomal large subunit biogenesis / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 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 / 5S rRNA binding / ribosomal large subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / 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 / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Leishmania major strain Friedlin (eukaryote) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||||||||||||||||||||
Authors | Rajan, K.S. / Yonath, A. | ||||||||||||||||||||||||
| Funding support | Israel, European Union, 2items
| ||||||||||||||||||||||||
Citation | Journal: J Med Chem / Year: 2025Title: -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 |
|
-
Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
|---|
-
Downloads & links
-
Download
| PDBx/mmCIF format | 9hl9.cif.gz | 5.3 MB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb9hl9.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9hl9.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9hl9_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
|---|---|---|---|---|
| Full document | 9hl9_full_validation.pdf.gz | 2.1 MB | Display | |
| Data in XML | 9hl9_validation.xml.gz | 375.6 KB | Display | |
| Data in CIF | 9hl9_validation.cif.gz | 637.4 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hl/9hl9 ftp://data.pdbj.org/pub/pdb/validation_reports/hl/9hl9 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 52247MC M: map data used to model this data C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
Components
+RNA chain , 12 types, 12 molecules L1L2L3L4L5L6L7L8S3S4S5S1
+Putative 60S ... , 24 types, 24 molecules LALELFLHLILJLLLNLOLQLSLTLULVLWLZLaLcLeLhLiLlLnLp
+Putative ribosomal protein ... , 7 types, 7 molecules LBLCLXLgLkSMSS
+60S ribosomal protein ... , 9 types, 9 molecules LDLGLPLRLYLbLdLfLo
+Putative 40S ribosomal protein ... , 14 types, 14 molecules LKSCSDSJSLSNSPSRSTSVSWSYScSd
+Ribosomal protein ... , 3 types, 3 molecules LMLjSU
+Ubiquitin-60S ribosomal protein ... , 2 types, 2 molecules LmSf
+Protein , 3 types, 3 molecules SASgSh
+40S ribosomal protein ... , 14 types, 14 molecules SBSESFSGSHSISKSOSQSXSZSaSbSe
+Non-polymers , 6 types, 1791 molecules 








+Details
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: 80S RIBOSOME WITH P/E-site tRNA AND mRNA / Type: RIBOSOME / Entity ID: #1-#50, #88, #51-#87 / Source: NATURAL |
|---|---|
| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Leishmania major strain Friedlin (eukaryote) |
| Buffer solution | pH: 7.6 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
|---|---|
| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| 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) |
-
Processing
| EM software |
| ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | ||||||||||||||||||||||||
| Refinement | Highest resolution: 2.5 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
| Refine LS restraints |
|
Movie
Controller
About Yorodumi



Leishmania major strain Friedlin (eukaryote)
Israel, European Union, 2items
Citation



PDBj
































FIELD EMISSION GUN