[English] 日本語
Yorodumi
- PDB-6bn8: Crystal structure of DDB1-CRBN-BRD4(BD1) complex bound to dBET55 ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6bn8
TitleCrystal structure of DDB1-CRBN-BRD4(BD1) complex bound to dBET55 PROTAC.
Components
  • Bromodomain-containing protein 4
  • DNA damage-binding protein 1,DNA damage-binding protein 1
  • Protein cereblon
KeywordsLIGASE / PROTAC / degrader / E3 ligase / CRBN
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 / Cul4-RING E3 ubiquitin ligase complex / 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 ...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 / Cul4-RING E3 ubiquitin ligase complex / 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 / 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 / viral release from host cell / P-TEFb complex binding / negative regulation of DNA damage checkpoint / host-mediated suppression of viral transcription / positive regulation of Wnt signaling pathway / ectopic germ cell programmed cell death / negative regulation of protein-containing complex assembly / positive regulation of viral genome replication / positive regulation of T-helper 17 cell lineage commitment / proteasomal protein catabolic process / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of gluconeogenesis / RNA polymerase II CTD heptapeptide repeat kinase activity / : / histone reader activity / condensed nuclear chromosome / nucleotide-excision repair / transcription coregulator activity / positive regulation of protein-containing complex assembly / positive regulation of transcription elongation by RNA polymerase II / Recognition of DNA damage by PCNA-containing replication complex / regulation of circadian rhythm / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Formation of Incision Complex in GG-NER / Wnt signaling pathway / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / positive regulation of protein catabolic process / cellular response to UV / p53 binding / rhythmic process / site of double-strand break / chromosome / Neddylation / regulation of inflammatory response / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / histone binding / proteasome-mediated ubiquitin-dependent protein catabolic process / Potential therapeutics for SARS / transmembrane transporter binding / damaged DNA 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 / protein-containing complex binding / chromatin / positive regulation of DNA-templated transcription / nucleolus / perinuclear region of cytoplasm / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / extracellular space / extracellular exosome / nucleoplasm / metal ion binding / nucleus / membrane / cytosol / cytoplasm
Similarity search - Function
Methane Monooxygenase Hydroxylase; Chain G, domain 1 - #1480 / LON domain-like / Peptide methionine sulfoxide reductase. / DNA polymerase; domain 1 - #910 / Metal Binding Protein, Guanine Nucleotide Exchange Factor; Chain A / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / Archaeosine Trna-guanine Transglycosylase; Chain: A, domain 4 / CULT domain / CULT domain profile. ...Methane Monooxygenase Hydroxylase; Chain G, domain 1 - #1480 / LON domain-like / Peptide methionine sulfoxide reductase. / DNA polymerase; domain 1 - #910 / Metal Binding Protein, Guanine Nucleotide Exchange Factor; Chain A / Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / Archaeosine Trna-guanine Transglycosylase; Chain: A, domain 4 / 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 / YVTN repeat-like/Quinoprotein amine dehydrogenase / Methane Monooxygenase Hydroxylase; Chain G, domain 1 / Beta Complex / 7 Propeller / Methylamine Dehydrogenase; Chain H / Bromodomain-like / Histone Acetyltransferase; Chain A / DNA polymerase; domain 1 / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Roll / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Up-down Bundle / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Bromodomain-containing protein 4 / DNA damage-binding protein 1 / Protein cereblon
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.99003499985 Å
AuthorsNowak, R.P. / DeAngelo, S.L. / Buckley, D. / Bradner, J.E. / Fischer, E.S.
Funding support United States, 5items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)NCI R01CA214608 United States
The Harvard University William F. Milton Fund United States
Friends of Dana Farber United States
the Claudia Adams Barr Program for Innovative Cancer Research United States
the Linde Family Foundation United States
CitationJournal: Nat. Chem. Biol. / Year: 2018
Title: Plasticity in binding confers selectivity in ligand-induced protein degradation.
Authors: Nowak, R.P. / DeAngelo, S.L. / Buckley, D. / He, Z. / Donovan, K.A. / An, J. / Safaee, N. / Jedrychowski, M.P. / Ponthier, C.M. / Ishoey, M. / Zhang, T. / Mancias, J.D. / Gray, N.S. / ...Authors: Nowak, R.P. / DeAngelo, S.L. / Buckley, D. / He, Z. / Donovan, K.A. / An, J. / Safaee, N. / Jedrychowski, M.P. / Ponthier, C.M. / Ishoey, M. / Zhang, T. / Mancias, J.D. / Gray, N.S. / Bradner, J.E. / Fischer, E.S.
History
DepositionNov 16, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 6, 2018Provider: repository / Type: Initial release
Revision 1.1Aug 1, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 7, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA damage-binding protein 1,DNA damage-binding protein 1
B: Protein cereblon
C: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)164,5524
Polymers164,4863
Non-polymers651
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5680 Å2
ΔGint-37 kcal/mol
Surface area56360 Å2
Unit cell
Length a, b, c (Å)115.204, 115.204, 597.135
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Space group name HallP652(x,y,z+1/12)

-
Components

#1: Protein DNA damage-binding protein 1,DNA damage-binding protein 1 / DDB p127 subunit / DNA damage-binding protein a / DDBa / Damage-specific DNA-binding protein 1 / ...DDB p127 subunit / DNA damage-binding protein a / DDBa / Damage-specific DNA-binding protein 1 / HBV X-associated protein 1 / XAP-1 / UV-damaged DNA-binding factor / UV-damaged DNA-binding protein 1 / UV-DDB 1 / XPE-binding factor / XPE-BF / Xeroderma pigmentosum group E-complementing protein / XPCe


Mass: 96425.586 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q16531
#2: Protein Protein cereblon


Mass: 53005.207 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN, AD-006 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q96SW2
#3: Protein Bromodomain-containing protein 4 / Protein HUNK1


Mass: 15055.370 Da / Num. of mol.: 1 / Mutation: T43M, D145A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.48 Å3/Da / Density % sol: 64.63 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 9% PEG20K, 18% PEG MME 550, 0.09M BICINE pH8.5, 9% Silver bullet G4 (0.16% w/v 3-Indolebutyric acid, 0.16% w/v Hexadecanedioic acid, 0.16% w/v Oxamic acid, 0.16% w/v Pyromellitic acid, 0.16% ...Details: 9% PEG20K, 18% PEG MME 550, 0.09M BICINE pH8.5, 9% Silver bullet G4 (0.16% w/v 3-Indolebutyric acid, 0.16% w/v Hexadecanedioic acid, 0.16% w/v Oxamic acid, 0.16% w/v Pyromellitic acid, 0.16% w/v Sebacic acid, 0.16% w/v Suberic acid, 0.02 M HEPES sodium pH 6.8)

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.97919 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 15, 2017
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97919 Å / Relative weight: 1
ReflectionResolution: 3.99→149.28 Å / Num. obs: 21315 / % possible obs: 100 % / Redundancy: 17 % / Biso Wilson estimate: 171.90188794 Å2 / CC1/2: 0.991 / Rmerge(I) obs: 0.28 / Rpim(I) all: 0.096 / Rrim(I) all: 0.296 / Net I/σ(I): 7.9
Reflection shellResolution: 3.99→4.31 Å / Redundancy: 16.1 % / Rmerge(I) obs: 2.227 / Mean I/σ(I) obs: 1.1 / Num. unique obs: 4219 / CC1/2: 0.452 / Rpim(I) all: 0.799 / Rrim(I) all: 2.367 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.12_2829refinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6BN7

6bn7


Resolution: 3.99003499985→99.769592696 Å / SU ML: 0.698541051771 / Cross valid method: FREE R-VALUE / σ(F): 1.3474641205 / Phase error: 33.6089833322
RfactorNum. reflection% reflectionSelection details
Rfree0.333448911462 1079 5.09130373236 %Random selection
Rwork0.288604646472 ---
obs0.290770625804 21193 99.9528368627 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 189.695887993 Å2
Refinement stepCycle: LAST / Resolution: 3.99003499985→99.769592696 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10290 0 1 0 10291
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0016251312879910505
X-RAY DIFFRACTIONf_angle_d0.45838254045814256
X-RAY DIFFRACTIONf_chiral_restr0.04186569175621617
X-RAY DIFFRACTIONf_plane_restr0.003857331058111838
X-RAY DIFFRACTIONf_dihedral_angle_d3.12602789036328
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.99-4.17160.4083847316391190.3753561675582421X-RAY DIFFRACTION99.725166863
4.1716-4.39160.3721750151351350.3631784642052426X-RAY DIFFRACTION100
4.3916-4.66670.3752042132581500.3359129827172438X-RAY DIFFRACTION100
4.6667-5.0270.370075718811410.3220265858642461X-RAY DIFFRACTION99.9615827891
5.027-5.53290.3182048698151320.3229878654852495X-RAY DIFFRACTION100
5.5329-6.33340.3968307106661240.3305680073162509X-RAY DIFFRACTION100
6.3334-7.97890.3511342744161490.2933069576812559X-RAY DIFFRACTION100
7.9789-99.80070.271713968911290.2290592298662805X-RAY DIFFRACTION99.931880109

+
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