[English] 日本語
Yorodumi
- EMDB-54690: Ternary PROTAC-mediated complex of BRD4-BD1/CRBN/DDB1 and JQ1-AcQ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-54690
TitleTernary PROTAC-mediated complex of BRD4-BD1/CRBN/DDB1 and JQ1-AcQ bifunctional degrader
Map datacomposite map
Sample
  • Complex: PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1 domain
    • Complex: Ligase sub-complex consisting of DDB1 (BPB deletion) and CRBN
      • Protein or peptide: DNA damage-binding protein 1
      • Protein or peptide: Protein cereblon
    • Complex: degradation target BRD4 (BD1 domain)
      • Protein or peptide: Bromodomain-containing protein 4
  • Ligand: ZINC ION
  • Ligand: ~{N}-[(2~{S})-1-[[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]amino]-1-oxidanylidene-propan-2-yl]-9-[2-[(9~{S})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,10,12-tetraen-9-yl]ethanoylamino]nonanamide
  • Ligand: water
KeywordsCryo-EM DDB1 (DNA Damage-Binding Protein 1) CRBN (Cereblon) BRD4 (bromodomain containing 4) Protein degradation cyclimid PROTACs / LIGASE
Function / homology
Function and homology information


negative regulation of monoatomic ion transmembrane transport / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex ...negative regulation of monoatomic ion transmembrane transport / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / locomotory exploration behavior / RNA polymerase II C-terminal domain binding / cullin family protein binding / P-TEFb complex binding / viral release from host cell / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of Wnt signaling pathway / positive regulation of G2/M transition of mitotic cell cycle / ectopic germ cell programmed cell death / negative regulation of protein-containing complex assembly / positive regulation of T-helper 17 cell lineage commitment / positive regulation of viral genome replication / proteasomal protein catabolic process / : / positive regulation of gluconeogenesis / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / transcription coregulator activity / nucleotide-excision repair / positive regulation of protein-containing complex assembly / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / positive regulation of transcription elongation by RNA polymerase II / Formation of TC-NER Pre-Incision Complex / Formation of Incision Complex in GG-NER / regulation of circadian rhythm / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Wnt signaling pathway / positive regulation of protein catabolic process / cellular response to UV / p53 binding / rhythmic process / site of double-strand break / Neddylation / chromosome / regulation of inflammatory response / ubiquitin-dependent protein catabolic process / histone binding / protein-macromolecule adaptor activity / damaged DNA binding / proteasome-mediated ubiquitin-dependent protein catabolic process / Potential therapeutics for SARS / transmembrane transporter binding / transcription coactivator activity / chromosome, telomeric region / positive regulation of canonical NF-kappaB signal transduction / transcription cis-regulatory region binding / protein ubiquitination / chromatin remodeling / DNA repair / protein serine/threonine kinase activity / apoptotic process / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / chromatin / positive regulation of DNA-templated transcription / protein-containing complex binding / nucleolus / perinuclear region of cytoplasm / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / extracellular space / DNA binding / extracellular exosome / nucleoplasm / metal ion binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon N-terminal domain profile. / Lon protease, N-terminal domain / Lon protease, N-terminal domain superfamily / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / RSE1/DDB1/CPSF1 second beta-propeller ...Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon N-terminal domain profile. / Lon protease, N-terminal domain / Lon protease, N-terminal domain superfamily / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / RSE1/DDB1/CPSF1 second beta-propeller / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / : / CPSF A subunit region / RSE1/DDB1/CPSF1 first beta-propeller / PUA-like superfamily / Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Bromodomain-containing protein 4 / DNA damage-binding protein 1 / Protein cereblon
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.55 Å
AuthorsPeter D / Fischer G / Arce Solano S / Kessler D
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: J Am Chem Soc / Year: 2025
Title: Enzyme-Activated Sugar-Coated Bifunctional Degraders.
Authors: Qian Zhu / Gerhard Fischer / Steven S Cheng / N Connor Payne / Daniel Peter / Alison C Mody / Silvia Arce-Solano / Dacheng Shen / Zhi Lin / Ralph Mazitschek / Dirk Kessler / Christina M Woo /
Abstract: Targeted protein degradation with compounds like proteolysis targeting chimeras (PROTACs) directs disease-associated proteins to the E3 ligase ubiquitin-proteasome system for removal. However, ...Targeted protein degradation with compounds like proteolysis targeting chimeras (PROTACs) directs disease-associated proteins to the E3 ligase ubiquitin-proteasome system for removal. However, commonly employed E3 ligases such as cereblon (CRBN) are broadly expressed. To metabolically gate PROTAC activity, we developed an enzymatic activation strategy by integrating an O-GlcNAc modification to the cyclimids, ligands derived from the natural motifs recognized by CRBN. These sugar-coated PROTACs (SCPs) were designed using structural analyses of representative cyclimid degraders complexed with CRBN and target protein BRD4. We found that glycosylation of the cyclimid reduced CRBN binding and complex formation with BRD4 until enzymatic removal of the O-GlcNAc moiety by O-GlcNAcase (OGA). The requirement for enzymatic activation is demonstrated by biochemical binding, cellular degradation, and cell viability assays in engineered and native cell lines. O-GlcNAc is thus an effective mechanism to gate targeted protein degradation modalities that motivates the development of similar strategies to enhance selectivity with other protein modifications.
History
DepositionAug 7, 2025-
Header (metadata) releaseOct 1, 2025-
Map releaseOct 1, 2025-
UpdateOct 1, 2025-
Current statusOct 1, 2025Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_54690.png

Downloads & links

-
Map

FileDownload / File: emd_54690.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationcomposite map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)X (Row.)Y (Col.)
0.75 Å/pix.
x 384 pix.
= 287.616 Å		0.75 Å/pix.
x 384 pix.
= 287.616 Å		0.75 Å/pix.
x 384 pix.
= 287.616 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.749 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 8.0
Minimum - Maximum-31.690529000000002 - 48.589545999999999
Average (Standard dev.)0.026635734 (±1.0844532)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderYXZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 287.616 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Sample components

-
Entire : PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1...

EntireName: PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1 domain
Components
  • Complex: PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1 domain
    • Complex: Ligase sub-complex consisting of DDB1 (BPB deletion) and CRBN
      • Protein or peptide: DNA damage-binding protein 1
      • Protein or peptide: Protein cereblon
    • Complex: degradation target BRD4 (BD1 domain)
      • Protein or peptide: Bromodomain-containing protein 4
  • Ligand: ZINC ION
  • Ligand: ~{N}-[(2~{S})-1-[[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]amino]-1-oxidanylidene-propan-2-yl]-9-[2-[(9~{S})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,10,12-tetraen-9-yl]ethanoylamino]nonanamide
  • Ligand: water

-
Supramolecule #1: PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1...

SupramoleculeName: PROTAC-mediated complex of DDB1 (BPB deletion), CRBN and BRD4 BD1 domain
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15 KDa

-
Supramolecule #2: Ligase sub-complex consisting of DDB1 (BPB deletion) and CRBN

SupramoleculeName: Ligase sub-complex consisting of DDB1 (BPB deletion) and CRBN
type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: degradation target BRD4 (BD1 domain)

SupramoleculeName: degradation target BRD4 (BD1 domain) / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: DNA damage-binding protein 1

MacromoleculeName: DNA damage-binding protein 1 / type: protein_or_peptide / ID: 1
Details: Deletion of beta-propeller B domain and replacement by short linker sequence
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 93.347078 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MSYNYVVTAQ KPTAVNGCVT GHFTSAEDLN LLIAKNTRLE IYVVTAEGLR PVKEVGMYGK IAVMELFRPK GESKDLLFIL TAKYNACIL EYKQSGESID IITRAHGNVQ DRIGRPSETG IIGIIDPECR MIGLRLYDGL FKVIPLDRDN KELKAFNIRL E ELHVIDVK ...String:
MSYNYVVTAQ KPTAVNGCVT GHFTSAEDLN LLIAKNTRLE IYVVTAEGLR PVKEVGMYGK IAVMELFRPK GESKDLLFIL TAKYNACIL EYKQSGESID IITRAHGNVQ DRIGRPSETG IIGIIDPECR MIGLRLYDGL FKVIPLDRDN KELKAFNIRL E ELHVIDVK FLYGCQAPTI CFVYQDPQGR HVKTYEVSLR EKEFNKGPWK QENVEAEASM VIAVPEPFGG AIIIGQESIT YH NGDKYLA IAPPIIKQST IVCHNRVDPN GSRYLLGDME GRLFMLLLEK EEQMDGTVTL KDLRVELLGE TSIAECLTYL DNG VVFVGS RLGDSQLVKL NVDSNEQGSY VVAMETFTNL GPIVDMCVVD LERQGQGQLV TCSGAFKEGS LRIIRNGIGG NGNS GEIQK LHIRTVPLYE SPRKICYQEV SQCFGVLSSR IEVQDTSGGT TALRPSASTQ ALSSSVSSSK LFSSSTAPHE TSFGE EVEV HNLLIIDQHT FEVLHAHQFL QNEYALSLVS CKLGKDPNTY FIVGTAMVYP EEAEPKQGRI VVFQYSDGKL QTVAEK EVK GAVYSMVEFN GKLLASINST VRLYEWTTEK ELRTECNHYN NIMALYLKTK GDFILVGDLM RSVLLLAYKP MEGNFEE IA RDFNPNWMSA VEILDDDNFL GAENAFNLFV CQKDSAATTD EERQHLQEVG LFHLGEFVNV FCHGSLVMQN LGETSTPT Q GSVLFGTVNG MIGLVTSLSE SWYNLLLDMQ NRLNKVIKSV GKIEHSFWRS FHTERKTEPA TGFIDGDLIE SFLDISRPK MQEVVANLQY DDGSGMKREA TADDLIKVVE ELTRIH

UniProtKB: DNA damage-binding protein 1

-
Macromolecule #2: Protein cereblon

MacromoleculeName: Protein cereblon / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 50.559559 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: SAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD TSLPTSHTYL GADMEEFHGR TLHDDDSCQV IPVLPQVMM ILIPGQTLPL QLFHPQEVSM VRNLIQKDRT FAVLAYSNVQ EREAQFGTTA EIYAYREEQD FGIEIVKVKA I GRQRFKVL ...String:
SAGEGDQQDA AHNMGNHLPL LPAESEEEDE MEVEDQDSKE AKKPNIINFD TSLPTSHTYL GADMEEFHGR TLHDDDSCQV IPVLPQVMM ILIPGQTLPL QLFHPQEVSM VRNLIQKDRT FAVLAYSNVQ EREAQFGTTA EIYAYREEQD FGIEIVKVKA I GRQRFKVL ELRTQSDGIQ QAKVQILPEC VLPSTMSAVQ LESLNKCQIF PSKPVSREDQ CSYKWWQKYQ KRKFHCANLT SW PRWLYSL YDAETLMDRI KKQLREWDEN LKDDSLPSNP IDFSYRVAAC LPIDDVLRIQ LLKIGSAIQR LRCELDIMNK CTS LCCKQC QETEITTKNE IFSLSLCGPM AAYVNPHGYV HETLTVYKAC NLNLIGRPST EHSWFPGYAW TVAQCKICAS HIGW KFTAT KKDMSPQKFW GLTRSALLPT IPDTEDEISP DKVILCL

UniProtKB: Protein cereblon

-
Macromolecule #3: Bromodomain-containing protein 4

MacromoleculeName: Bromodomain-containing protein 4 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15.09938 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
SMNPPPPETS NPNKPKRQTN QLQYLLRVVL KTLWKHQFAW PFQQPVDAVK LNLPDYYKII KTPMDMGTIK KRLENNYYWN AQECIQDFN TMFTNCYIYN KPGDDIVLMA EALEKLFLQK INELPTEE

UniProtKB: Bromodomain-containing protein 4

-
Macromolecule #4: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

-
Macromolecule #5: ~{N}-[(2~{S})-1-[[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]am...

MacromoleculeName: ~{N}-[(2~{S})-1-[[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]amino]-1-oxidanylidene-propan-2-yl]-9-[2-[(9~{S})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0. ...Name: ~{N}-[(2~{S})-1-[[(3~{S})-2,6-bis(oxidanylidene)piperidin-3-yl]amino]-1-oxidanylidene-propan-2-yl]-9-[2-[(9~{S})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,10,12-tetraen-9-yl]ethanoylamino]nonanamide
type: ligand / ID: 5 / Number of copies: 1 / Formula: A1JM8
Molecular weightTheoretical: 739.327 Da

-
Macromolecule #6: water

MacromoleculeName: water / type: ligand / ID: 6 / Number of copies: 89 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.3 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
100.0 mMNaClsodium chloride
0.25 mMTCEPTris(2-carboxyethyl)phosphine
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 3 / Number real images: 38923 / 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: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 165000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.55 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 158212
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

+
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