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- EMDB-52259: CRYO-EM FOCUSED REFINEMENT MAP OF LEISHMANIA MAJOR 80S RIBOSOME W... -

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Basic information

Entry
Database: EMDB / ID: EMD-52259
TitleCRYO-EM FOCUSED REFINEMENT MAP OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site tRNA AND mRNA : LM14Cs1H3 sKO STRAIN
Map dataBody 1 of focused refined map
Sample
  • Complex: 80S RIBOSOME WITH P/E-site tRNA AND mRNA
KeywordsCRYO-EM / LEISHMANIA MAJOR / 80S / RIBOSOME / LM14Cs1H3 / snoRNA
Biological speciesLeishmania major strain Friedlin (eukaryote)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.5 Å
AuthorsRajan KS / Yonath A
Funding support Israel, European Union, 2 items
OrganizationGrant numberCountry
Israel Science Foundation Israel
European Research Council (ERC)European Union
CitationJournal: J Med Chem / Year: 2025
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
DepositionDec 5, 2024-
Header (metadata) releaseOct 15, 2025-
Map releaseOct 15, 2025-
UpdateOct 22, 2025-
Current statusOct 22, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52259.png

Downloads & links

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Map

FileDownload / File: emd_52259.map.gz / Format: CCP4 / Size: 1000 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationBody 1 of focused refined map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.79 Å/pix.
x 640 pix.
= 507.52 Å		0.79 Å/pix.
x 640 pix.
= 507.52 Å		0.79 Å/pix.
x 640 pix.
= 507.52 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.793 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.005
Minimum - Maximum-0.025154762 - 0.048917715
Average (Standard dev.)-0.00029625336 (±0.0017972469)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions640640640
Spacing640640640
CellA=B=C: 507.52 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Half map 1 for Body 2 of focused refined map

Fileemd_52259_additional_1.map
AnnotationHalf map 1 for Body 2 of focused refined map
Projections & Slices
AxesZYX

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Additional map: Body 3 of focused refined map

Fileemd_52259_additional_2.map
AnnotationBody 3 of focused refined map
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Additional map: Body 2 of focused refined map

Fileemd_52259_additional_3.map
AnnotationBody 2 of focused refined map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Half map 1 for Body 3 of focused refined map

Fileemd_52259_additional_4.map
AnnotationHalf map 1 for Body 3 of focused refined map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Half map 2 for Body 3 of focused refined map

Fileemd_52259_additional_5.map
AnnotationHalf map 2 for Body 3 of focused refined map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Additional map: Half map 2 for Body 2 of focused refined map

Fileemd_52259_additional_6.map
AnnotationHalf map 2 for Body 2 of focused refined map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map 1 for Body 1 of focused refined map

Fileemd_52259_half_map_1.map
AnnotationHalf map 1 for Body 1 of focused refined map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map 2 for Body 1 of focused refined map

Fileemd_52259_half_map_2.map
AnnotationHalf map 2 for Body 1 of focused refined map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : 80S RIBOSOME WITH P/E-site tRNA AND mRNA

EntireName: 80S RIBOSOME WITH P/E-site tRNA AND mRNA
Components
  • Complex: 80S RIBOSOME WITH P/E-site tRNA AND mRNA

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Supramolecule #1: 80S RIBOSOME WITH P/E-site tRNA AND mRNA

SupramoleculeName: 80S RIBOSOME WITH P/E-site tRNA AND mRNA / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#88
Source (natural)Organism: Leishmania major strain Friedlin (eukaryote)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.6
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.0018 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

8rxh

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 138498
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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