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Yorodumi- EMDB-52247: CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site ... -
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Basic information
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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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Keywords | CRYO-EM / LEISHMANIA MAJOR / 80S / RIBOSOME / 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 | single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
Authors | Rajan KS / Yonath A | |||||||||
| Funding support | Israel, European Union, 2 items
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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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_52247.map.gz | 67.3 MB | EMDB map data format | |
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| Header (meta data) | emd-52247-v30.xml emd-52247.xml | 112.5 KB 112.5 KB | Display Display | EMDB header |
| Images | emd_52247.png | 61.3 KB | ||
| Filedesc metadata | emd-52247.cif.gz | 22.2 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-52247 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-52247 | HTTPS FTP |
-Validation report
| Summary document | emd_52247_validation.pdf.gz | 457 KB | Display | EMDB validaton report |
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| Full document | emd_52247_full_validation.pdf.gz | 456.6 KB | Display | |
| Data in XML | emd_52247_validation.xml.gz | 8.4 KB | Display | |
| Data in CIF | emd_52247_validation.cif.gz | 9.8 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-52247 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-52247 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9hl9MC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_52247.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.8245 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : 80S RIBOSOME WITH P/E-site tRNA AND mRNA
+Supramolecule #1: 80S RIBOSOME WITH P/E-site tRNA AND mRNA
+Macromolecule #1: LSUa_rRNA
+Macromolecule #2: LSUb_rRNA
+Macromolecule #3: SR1_rRNA
+Macromolecule #4: SR2_rRNA
+Macromolecule #5: SR4_rRNA
+Macromolecule #6: SR6_rRNA
+Macromolecule #7: 5.8S_rRNA
+Macromolecule #8: 5S_rRNA
+Macromolecule #51: P-site_tRNA
+Macromolecule #52: E-site_tRNA
+Macromolecule #53: mRNA
+Macromolecule #88: SSU_rRNA
+Macromolecule #9: Putative 60S ribosomal protein L2
+Macromolecule #10: Putative ribosomal protein L3
+Macromolecule #11: Putative ribosomal protein L1a
+Macromolecule #12: 60S ribosomal protein L11
+Macromolecule #13: Putative 60S ribosomal protein L9
+Macromolecule #14: Putative 60S ribosomal protein L6
+Macromolecule #15: 60S ribosomal protein L7a
+Macromolecule #16: Putative 60S ribosomal protein L13a
+Macromolecule #17: Putative 60S ribosomal protein L13
+Macromolecule #18: Putative 60S ribosomal protein L23
+Macromolecule #19: Putative 40S ribosomal protein L14
+Macromolecule #20: Putative 60S ribosomal protein L27A/L29
+Macromolecule #21: Ribosomal protein L15
+Macromolecule #22: Putative 60S ribosomal protein L10
+Macromolecule #23: Putative 60S ribosomal protein L5
+Macromolecule #24: 60S ribosomal protein L18
+Macromolecule #25: Putative 60S ribosomal protein L19
+Macromolecule #26: 60S ribosomal protein L18a
+Macromolecule #27: Putative 60S ribosomal protein L21
+Macromolecule #28: Putative 60S ribosomal protein L17
+Macromolecule #29: Putative 60S ribosomal protein L22
+Macromolecule #30: Putative 60S ribosomal protein L23a
+Macromolecule #31: Putative 60S ribosomal protein L26
+Macromolecule #32: Putative ribosomal protein L24
+Macromolecule #33: 60S ribosomal protein L27
+Macromolecule #34: Putative 60S ribosomal protein L28
+Macromolecule #35: Putative 60S ribosomal protein L35
+Macromolecule #36: 60S ribosomal protein L29
+Macromolecule #37: Putative 60S ribosomal protein L7
+Macromolecule #38: 60S ribosomal protein L30
+Macromolecule #39: Putative 60S ribosomal subunit protein L31
+Macromolecule #40: 60S ribosomal protein L32
+Macromolecule #41: Putative ribosomal protein l35a
+Macromolecule #42: Putative 60S ribosomal protein L34
+Macromolecule #43: Putative 60S Ribosomal protein L36
+Macromolecule #44: Ribosomal protein L37
+Macromolecule #45: Putative ribosomal protein L38
+Macromolecule #46: Putative 60S ribosomal protein L39
+Macromolecule #47: Ubiquitin-60S ribosomal protein L40
+Macromolecule #48: Putative 60S ribosomal protein L41
+Macromolecule #49: 60S ribosomal protein L37a
+Macromolecule #50: Putative 60S ribosomal protein L44
+Macromolecule #54: Small ribosomal subunit protein eS1
+Macromolecule #55: 40S ribosomal protein SA
+Macromolecule #56: Putative 40S ribosomal protein S3
+Macromolecule #57: Putative 40S ribosomal protein S9
+Macromolecule #58: 40S ribosomal protein S4
+Macromolecule #59: 40S ribosomal protein S2
+Macromolecule #60: 40S ribosomal protein S6
+Macromolecule #61: 40S ribosomal protein S5
+Macromolecule #62: 40S ribosomal protein S7
+Macromolecule #63: Putative 40S ribosomal protein S15A
+Macromolecule #64: 40S ribosomal protein S8
+Macromolecule #65: Putative 40S ribosomal protein S16
+Macromolecule #66: Putative ribosomal protein S20
+Macromolecule #67: Putative 40S ribosomal protein S10
+Macromolecule #68: 40S ribosomal protein S14
+Macromolecule #69: Putative 40S ribosomal protein S23
+Macromolecule #70: 40S ribosomal protein S12
+Macromolecule #71: Putative 40S ribosomal protein S18
+Macromolecule #72: Putative ribosomal protein S29
+Macromolecule #73: Putative 40S ribosomal protein S13
+Macromolecule #74: Ribosomal protein S17 family protein
+Macromolecule #75: Putative 40S ribosomal protein S17
+Macromolecule #76: Putative 40S ribosomal protein S15
+Macromolecule #77: 40S ribosomal protein S19-like protein
+Macromolecule #78: Putative 40S ribosomal protein S21
+Macromolecule #79: 40S ribosomal protein S24
+Macromolecule #80: 40S ribosomal protein S25
+Macromolecule #81: 40S ribosomal protein S26
+Macromolecule #82: Putative 40S ribosomal protein S27-1
+Macromolecule #83: Putative 40S ribosomal protein S33
+Macromolecule #84: 40S ribosomal protein S30
+Macromolecule #85: Ubiquitin-60S ribosomal protein L40
+Macromolecule #86: Guanine nucleotide-binding protein subunit beta-like protein
+Macromolecule #87: Putative RNA binding protein
+Macromolecule #89: POTASSIUM ION
+Macromolecule #90: SODIUM ION
+Macromolecule #91: MAGNESIUM ION
+Macromolecule #92: [(2R,3S,4S)-4-oxidanyl-2-[(4-prop-2-ynoxyphenyl)methyl]pyrrolidin...
+Macromolecule #93: ZINC ION
+Macromolecule #94: water
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.6 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.0018 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



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










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Processing
FIELD EMISSION GUN

