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- EMDB-46598: Human-yeast chimeric Sec complex bound to KZR-261 inhibitor -

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Basic information

Entry
Database: EMDB / ID: EMD-46598
TitleHuman-yeast chimeric Sec complex bound to KZR-261 inhibitor
Map dataSharpened map
Sample
  • Complex: Human-yeast chimeric Sec complex
KeywordsSec61 / translocon / translocation / endoplasmic reticulum / secretion / MEMBRANE PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsPark E / Wang L
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J.Pharmacol.Exp.Ther. / Year: 2025
Title: Pre-clinical characterization of novel multi-client inhibitors of Sec61 with broad anti-tumor activity
Authors: Lowe E / Anderl JL / Bade D / Delgado-Martin C / Dong C / Fan RA / Fang Y / Jiang J / Johnson HW / Kempema A / McGilvray P / McMinn D / Millare B / Muchamuel T / Poweleit N / Qian Y / Rehan ...Authors: Lowe E / Anderl JL / Bade D / Delgado-Martin C / Dong C / Fan RA / Fang Y / Jiang J / Johnson HW / Kempema A / McGilvray P / McMinn D / Millare B / Muchamuel T / Poweleit N / Qian Y / Rehan S / Scapin G / Sugahara A / Tranter D / Tuch B / Wang J / Wang L / Whang JA / Zuno-Mitchell P / Paavilainen VO / Park E / Taunton J / Kirk CJ / Anand NK
History
DepositionAug 15, 2024-
Header (metadata) releaseJun 25, 2025-
Map releaseJun 25, 2025-
UpdateJun 25, 2025-
Current statusJun 25, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_46598.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.15 Å/pix.
x 256 pix.
= 294.4 Å
1.15 Å/pix.
x 256 pix.
= 294.4 Å
1.15 Å/pix.
x 256 pix.
= 294.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.15 Å
Density
Contour LevelBy AUTHOR: 1.46
Minimum - Maximum-8.370621 - 14.204388
Average (Standard dev.)0.009153856 (±0.23223644)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 294.4 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_46598_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Additional map: Averaged map

Fileemd_46598_additional_1.map
AnnotationAveraged map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map 1

Fileemd_46598_half_map_1.map
AnnotationHalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: Half map 2

Fileemd_46598_half_map_2.map
AnnotationHalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Human-yeast chimeric Sec complex

EntireName: Human-yeast chimeric Sec complex
Components
  • Complex: Human-yeast chimeric Sec complex

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Supramolecule #1: Human-yeast chimeric Sec complex

SupramoleculeName: Human-yeast chimeric Sec complex / type: complex / ID: 1 / Parent: 0
Details: Contains human Sec61 complex, human-yeast chimeric Sec63, yeast Sec71, and yeast Sec72
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 191 KDa

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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

Concentration7.3 mg/mL
BufferpH: 7.5
Details: 25mM Tris-HCl pH 7.5, 100mM NaCl, 2mM DTT, 1mM EDTA, 0.04% beta-dodecylmaltoside, 0.008% cholesteryl hemisuccinate
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
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: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.5) / Number images used: 351170
Initial angle assignmentType: RANDOM ASSIGNMENT / Software - Name: cryoSPARC (ver. 4.5)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.5)
FSC plot (resolution estimation)

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