[English] 日本語
Yorodumi
- PDB-8rqc: Crystal structure of CRBN-midi in complex with mezigdomide and IK... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8rqc
TitleCrystal structure of CRBN-midi in complex with mezigdomide and IKZF1 ZF2
Components
  • DNA-binding protein Ikaros
  • Protein cereblon
KeywordsLIGASE / E3 ligase / PROTAC / TPD / molecular glue / targeted protein degradation
Function / homology
Function and homology information


lymphocyte differentiation / negative regulation of monoatomic ion transmembrane transport / NOTCH3 Intracellular Domain Regulates Transcription / Cul4A-RING E3 ubiquitin ligase complex / mesoderm development / locomotory exploration behavior / positive regulation of Wnt signaling pathway / pericentric heterochromatin / negative regulation of protein-containing complex assembly / erythrocyte differentiation ...lymphocyte differentiation / negative regulation of monoatomic ion transmembrane transport / NOTCH3 Intracellular Domain Regulates Transcription / Cul4A-RING E3 ubiquitin ligase complex / mesoderm development / locomotory exploration behavior / positive regulation of Wnt signaling pathway / pericentric heterochromatin / negative regulation of protein-containing complex assembly / erythrocyte differentiation / positive regulation of protein-containing complex assembly / chromatin organization / Potential therapeutics for SARS / proteasome-mediated ubiquitin-dependent protein catabolic process / transmembrane transporter binding / protein ubiquitination / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein domain specific binding / negative regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / perinuclear region of cytoplasm / protein-containing complex / DNA binding / zinc ion binding / nucleoplasm / metal ion binding / identical protein binding / nucleus / membrane / cytoplasm / cytosol
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) ...: / 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) / PUA-like superfamily / Zinc finger, C2H2 type / zinc finger / Zinc finger C2H2 type domain profile. / Zinc finger C2H2 superfamily / Zinc finger C2H2 type domain signature. / Zinc finger C2H2-type
Similarity search - Domain/homology
Mezigdomide / DNA-binding protein Ikaros / Protein cereblon
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsFurihata, H. / Kroupova, A. / Zollman, D. / Ciulli, A.
Funding support1items
OrganizationGrant numberCountry
Other private
CitationJournal: Nat Commun / Year: 2024
Title: Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders.
Authors: Kroupova, A. / Spiteri, V.A. / Rutter, Z.J. / Furihata, H. / Darren, D. / Ramachandran, S. / Chakraborti, S. / Haubrich, K. / Pethe, J. / Gonzales, D. / Wijaya, A.J. / Rodriguez-Rios, M. / ...Authors: Kroupova, A. / Spiteri, V.A. / Rutter, Z.J. / Furihata, H. / Darren, D. / Ramachandran, S. / Chakraborti, S. / Haubrich, K. / Pethe, J. / Gonzales, D. / Wijaya, A.J. / Rodriguez-Rios, M. / Sturbaut, M. / Lynch, D.M. / Farnaby, W. / Nakasone, M.A. / Zollman, D. / Ciulli, A.
History
DepositionJan 17, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 25, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2024Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein cereblon
B: DNA-binding protein Ikaros
D: Protein cereblon
E: DNA-binding protein Ikaros
hetero molecules


Theoretical massNumber of molelcules
Total (without water)84,39410
Polymers82,9974
Non-polymers1,3976
Water3,225179
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)53.585, 142.842, 56.693
Angle α, β, γ (deg.)90.000, 112.341, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and (resid 64 through 70 or (resid 71...
d_2ens_1(chain "D" and (resid 64 through 67 or (resid 70...
d_1ens_2(chain "B" and (resid 144 through 155 or (resid 156...
d_2ens_2(chain "E" and (resid 144 through 164 or (resid 165...
d_1ens_3chain "C"
d_2ens_3chain "F"

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ens_1METMETVALVALAA64 - 12825 - 89
d_12ens_1GLUGLULYSLYSAA132 - 31793 - 220
d_13ens_1THRTHRTHRTHRAA319 - 425222 - 328
d_21ens_1METMETPHEPHEDC64 - 6725 - 28
d_22ens_1ARGARGVALVALDC70 - 12831 - 89
d_23ens_1GLUGLULYSLYSDC132 - 31793 - 220
d_24ens_1THRTHRTHRTHRDC319 - 425222 - 328
d_11ens_2PROPROGLUGLUBB144 - 1706 - 32
d_21ens_2PROPROGLUGLUED144 - 1706 - 32
d_11ens_3QFCQFCQFCQFCAF602
d_21ens_3QFCQFCQFCQFCDI602

NCS ensembles :
ID
ens_1
ens_2
ens_3

NCS oper:
IDCodeMatrixVector
1given(0.999938374876, 0.0074499040083, 0.0082307581618), (-0.00870572470389, 0.0661441204367, 0.997772101078), (0.00688889011604, -0.997782267963, 0.0662049011105)4.05952435032, 27.1920133249, 10.0610537214
2given(0.996011917047, -0.0886125562329, -0.0103959596902), (0.0113944885167, 0.010770082646, 0.999877077921), (-0.0884896984482, -0.996007941835, 0.0117368254175)2.39352961466, 26.6777646986, 9.28221081231
3given(0.996651582245, -0.0706976093748, 0.0410788465999), (-0.0374941749046, 0.0513057497306, 0.997978911046), (-0.0726623042403, -0.9961774782, 0.048483208116)3.00178193825, 26.9990169492, 10.1637717186

-
Components

#1: Protein Protein cereblon


Mass: 37478.805 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CRBN, AD-006 / Production host: Escherichia coli (E. coli) / References: UniProt: Q96SW2
#2: Protein/peptide DNA-binding protein Ikaros / Ikaros family zinc finger protein 1 / Lymphoid transcription factor LyF-1


Mass: 4019.614 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IKZF1, IK1, IKAROS, LYF1, ZNFN1A1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q13422
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-QFC / Mezigdomide


Mass: 567.610 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C32H30FN5O4 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 179 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.36 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.2 M ammonium sulphate, 25% (w/v) PEG 3350, and 0.1 M HEPES pH 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.957 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Sep 23, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.957 Å / Relative weight: 1
ReflectionResolution: 2.15→52.44 Å / Num. obs: 42776 / % possible obs: 97.56 % / Redundancy: 7.1 % / Biso Wilson estimate: 50.06 Å2 / CC1/2: 0.996 / CC star: 0.999 / Rmerge(I) obs: 0.2004 / Rpim(I) all: 0.08074 / Rrim(I) all: 0.2162 / Net I/σ(I): 6.12
Reflection shellResolution: 2.15→2.227 Å / Redundancy: 7.2 % / Rmerge(I) obs: 3.696 / Mean I/σ(I) obs: 0.32 / Num. unique obs: 4266 / CC1/2: 0.343 / CC star: 0.715 / Rpim(I) all: 1.477 / Rrim(I) all: 3.984 / % possible all: 80.1

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
xia2data scaling
PHASERphasing
Cootmodel building
xia2data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→52.44 Å / SU ML: 0.4658 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 40.4494
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2859 1974 4.73 %
Rwork0.2607 39801 -
obs0.2619 41775 97.45 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 62.45 Å2
Refinement stepCycle: LAST / Resolution: 2.15→52.44 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5033 0 88 179 5300
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01035237
X-RAY DIFFRACTIONf_angle_d1.46127135
X-RAY DIFFRACTIONf_chiral_restr0.0881805
X-RAY DIFFRACTIONf_plane_restr0.0073919
X-RAY DIFFRACTIONf_dihedral_angle_d17.03351849
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAX-RAY DIFFRACTIONTorsion NCS1.30461395183
ens_2d_2BBX-RAY DIFFRACTIONTorsion NCS1.55217381539
ens_3d_2FAX-RAY DIFFRACTIONTorsion NCS1.14823804695
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.15-2.20.4419920.48042069X-RAY DIFFRACTION71.2
2.2-2.260.47211410.46232874X-RAY DIFFRACTION97.67
2.26-2.330.43191440.44362845X-RAY DIFFRACTION98.78
2.33-2.40.44021410.41422885X-RAY DIFFRACTION99.47
2.4-2.490.36421700.37932860X-RAY DIFFRACTION99.57
2.49-2.590.41011560.34462920X-RAY DIFFRACTION99.45
2.59-2.710.35031300.32152910X-RAY DIFFRACTION99.48
2.71-2.850.32521360.28892899X-RAY DIFFRACTION99.57
2.85-3.030.32841360.28572912X-RAY DIFFRACTION99.74
3.03-3.260.29681380.27072911X-RAY DIFFRACTION99.74
3.26-3.590.27651290.24432934X-RAY DIFFRACTION99.74
3.59-4.110.2741560.21442915X-RAY DIFFRACTION100
4.11-5.180.20961650.19642907X-RAY DIFFRACTION99.93
5.18-52.440.24911400.23022960X-RAY DIFFRACTION99.68

+
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