[English] 日本語
Yorodumi
- EMDB-71123: CD73-Sym024 focused map 1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-71123
TitleCD73-Sym024 focused map 1
Map data
Sample
  • Complex: CD73 dimer bound to antibody Sym024
KeywordsAntigen-Antibody Complex / Drug Target / HYDROLASE
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.66 Å
AuthorsArmbruster E / Bansia H / Des Georges A
Funding support1 items
OrganizationGrant numberCountry
Other private
CitationJournal: Clin Cancer Res / Year: 2026
Title: Sym024 interacts with a unique epitope on the CD73 homodimer, favoring effective bivalent binding to improve anti-PD1 therapy.
Authors: Janus S Jakobsen / Michael M Grandal / Randi W Hansen / Harsh Bansia / Emily Armbruster / Isabelle Theret / Niels Jørgen Ø Skartved / Rikke Hald / Maria C Melander / Anne Worsaae / Matteo ...Authors: Janus S Jakobsen / Michael M Grandal / Randi W Hansen / Harsh Bansia / Emily Armbruster / Isabelle Theret / Niels Jørgen Ø Skartved / Rikke Hald / Maria C Melander / Anne Worsaae / Matteo Riva / Kristian Reckzeh / Laurent Vuillard / Johan Lantto / Amedee des Georges / Camilla Fröhlich /
Abstract: PURPOSE: Adenosine signaling may be a central immune suppressive mechanism in several cancers, and blockade of the rate-limiting CD73 AMP-to-adenosine enzyme has been demonstrated to improve clinical ...PURPOSE: Adenosine signaling may be a central immune suppressive mechanism in several cancers, and blockade of the rate-limiting CD73 AMP-to-adenosine enzyme has been demonstrated to improve clinical efficacy of PD(L)-1 immune therapy. However, deep inhibition of CD73 activity could prove difficult in tumor environments with a constant AMP supply and high CD73 levels. Here, we sought to identify, characterize, and benchmark a novel antagonistic anti-CD73 antibody, Sym024 (S95024), and to structurally decode its mode of action.
EXPERIMENTAL DESIGN: Sym024, selected via functional antibody repertoire screening, was tested against benchmark anti-CD73 antibodies in primary cell, cell line in vitro binding, CD73 enzymatic ...EXPERIMENTAL DESIGN: Sym024, selected via functional antibody repertoire screening, was tested against benchmark anti-CD73 antibodies in primary cell, cell line in vitro binding, CD73 enzymatic activity, and T cell activation assays. Its in vivo tumor growth inhibition was examined in transplanted human or mouse tumors in immunocompetent or immunodeficient mice, and intra-tumoral enzymatic inhibition and immune cell recruitment were assessed. We investigated Sym024-CD73 interaction using surface plasmon resonance, cryo-electron microscopy, site-directed mutagenesis, and population level complex formation through size-exclusion-chromatography with light scatter mass detection. Preclinical safety and pharmacokinetics were assessed in monkeys.
RESULTS: Sym024 effectively blocked CD73 across a large range of enzyme expression levels, comparing favorably to benchmark anti-CD73 antibodies; it improved the efficacy of PD-1 blockade in vitro as ...RESULTS: Sym024 effectively blocked CD73 across a large range of enzyme expression levels, comparing favorably to benchmark anti-CD73 antibodies; it improved the efficacy of PD-1 blockade in vitro as well as in vivo. Our structural data indicate that a unique one-to-one Sym024-CD73 interaction engenders this comprehensive inhibition. No pre-clinical safety flags were observed, and the pharmacokinetics profile of Sym024 supported a standard clinical dosing regimen.
CONCLUSIONS: The comprehensive CD73 inhibition exhibited by Sym024 may improve the efficacy of anti-PD(L)-1/anti-CD73 combination treatment.
History
DepositionJun 10, 2025-
Header (metadata) releaseJan 7, 2026-
Map releaseJan 7, 2026-
UpdateJan 21, 2026-
Current statusJan 21, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_71123.png

Downloads & links

-
Map

FileDownload / File: emd_71123.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 270.88 Å		0.85 Å/pix.
x 320 pix.
= 270.88 Å		0.85 Å/pix.
x 320 pix.
= 270.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8465 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.735
Minimum - Maximum-2.6835117 - 4.504663
Average (Standard dev.)0.00047211212 (±0.07890441)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 270.88 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_71123_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_71123_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : CD73 dimer bound to antibody Sym024

EntireName: CD73 dimer bound to antibody Sym024
Components
  • Complex: CD73 dimer bound to antibody Sym024

-
Supramolecule #1: CD73 dimer bound to antibody Sym024

SupramoleculeName: CD73 dimer bound to antibody Sym024 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Homo sapiens (human)

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.5 mg/mL
BufferpH: 5.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS TITAN THEMIS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.66 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 286779
Initial angle assignmentType: COMMON LINE
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more