[English] 日本語
Yorodumi
- PDB-6uml: Structural Basis for Thalidomide Teratogenicity Revealed by the C... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6uml
TitleStructural Basis for Thalidomide Teratogenicity Revealed by the Cereblon-DDB1-SALL4-Pomalidomide Complex
Components
  • DNA damage-binding protein 1
  • Protein cereblon
  • Sal-like protein 4
KeywordsLIGASE / CELMoD / cereblon-CRL4 / ubiquitin ligase / C2H2 zinc finger
Function / homology
Function and homology information


POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / negative regulation of monoatomic ion transmembrane transport / Transcriptional regulation of pluripotent stem cells / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / embryonic limb morphogenesis / biological process involved in interaction with symbiont ...POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / negative regulation of monoatomic ion transmembrane transport / Transcriptional regulation of pluripotent stem cells / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / embryonic limb morphogenesis / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / inner cell mass cell proliferation / ventricular septum development / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / locomotory exploration behavior / cullin family protein binding / somatic stem cell population maintenance / positive regulation of Wnt signaling pathway / viral release from host cell / ectopic germ cell programmed cell death / negative regulation of protein-containing complex assembly / positive regulation of viral genome replication / heterochromatin / positive regulation of gluconeogenesis / Regulation of PTEN gene transcription / neural tube closure / proteasomal protein catabolic process / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / positive regulation of protein-containing complex assembly / DNA Damage Recognition in GG-NER / regulation of circadian rhythm / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Wnt signaling pathway / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / positive regulation of protein catabolic process / rhythmic process / cellular response to UV / protein-macromolecule adaptor activity / site of double-strand break / Neddylation / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / transmembrane transporter binding / Potential therapeutics for SARS / chromosome, telomeric region / damaged DNA binding / protein ubiquitination / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / intracellular membrane-bounded organelle / DNA repair / apoptotic process / DNA damage response / protein-containing complex binding / nucleolus / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / extracellular space / extracellular exosome / nucleoplasm / membrane / metal ion binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon protease, N-terminal domain superfamily / Lon N-terminal domain profile. / Lon protease, N-terminal domain / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / Cleavage/polyadenylation specificity factor, A subunit, N-terminal ...Yippee/Mis18/Cereblon / Yippee zinc-binding/DNA-binding /Mis18, centromere assembly / CULT domain / CULT domain profile. / Lon protease, N-terminal domain superfamily / Lon N-terminal domain profile. / Lon protease, N-terminal domain / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / CPSF A subunit region / 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 / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
S-Pomalidomide / DNA damage-binding protein 1 / Protein cereblon / Sal-like protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.58 Å
AuthorsClayton, T.L. / Matyskiela, M.E. / Pagarigan, B.E. / Tran, E.T. / Chamberlain, P.P.
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2020
Title: Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.
Authors: Matyskiela, M.E. / Clayton, T. / Zheng, X. / Mayne, C. / Tran, E. / Carpenter, A. / Pagarigan, B. / McDonald, J. / Rolfe, M. / Hamann, L.G. / Lu, G. / Chamberlain, P.P.
History
DepositionOct 9, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 15, 2020Provider: repository / Type: Initial release
Revision 1.1Apr 22, 2020Group: 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 1.2Oct 11, 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
C: Protein cereblon
E: Sal-like protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)177,3596
Polymers176,9553
Non-polymers4043
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)77.409, 127.725, 110.174
Angle α, β, γ (deg.)90.000, 109.694, 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

-
Components

#1: Protein 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: 127097.469 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DDB1, XAP1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q16531
#2: Protein Protein cereblon


Mass: 46596.566 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96SW2
#3: Protein/peptide Sal-like protein 4 / Zinc finger protein 797 / Zinc finger protein SALL4


Mass: 3260.777 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SALL4, ZNF797 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UJQ4
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical ChemComp-Y70 / S-Pomalidomide


Mass: 273.244 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H11N3O4 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.9 Å3/Da / Density % sol: 57.56 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 10% PEG MME 500, 8% PEG 20K, 210mM calcium acetate, 100mM tris pH 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97931 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Feb 6, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97931 Å / Relative weight: 1
ReflectionResolution: 3.58→38.7 Å / Num. obs: 23629 / % possible obs: 98.42 % / Redundancy: 3.4 % / Biso Wilson estimate: 79.26 Å2 / CC1/2: 0.964 / Rmerge(I) obs: 0.1637 / Rpim(I) all: 0.1042 / Rrim(I) all: 0.1948 / Net I/σ(I): 5.04
Reflection shellResolution: 3.58→3.64 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.5699 / Num. unique obs: 2336 / CC1/2: 0.734 / Rpim(I) all: 0.3551 / Rrim(I) all: 0.6734 / % possible all: 98.11

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
xia2data reduction
DIALSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4TZ4

4tz4


Resolution: 3.58→38.7 Å / SU ML: 0.5122 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.413
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2671 1092 4.63 %
Rwork0.2038 22484 -
obs0.2066 23576 98.47 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 85.16 Å2
Refinement stepCycle: LAST / Resolution: 3.58→38.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms11082 0 22 0 11104
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.004411319
X-RAY DIFFRACTIONf_angle_d0.679115386
X-RAY DIFFRACTIONf_chiral_restr0.0461806
X-RAY DIFFRACTIONf_plane_restr0.00561959
X-RAY DIFFRACTIONf_dihedral_angle_d6.33476736
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.58-3.740.35141380.28122775X-RAY DIFFRACTION98.15
3.74-3.940.34051240.2472851X-RAY DIFFRACTION99.33
3.94-4.180.29531650.21592763X-RAY DIFFRACTION99.39
4.18-4.510.21951390.17642806X-RAY DIFFRACTION98.4
4.51-4.960.22861170.16412802X-RAY DIFFRACTION97.85
4.96-5.670.26021330.18232859X-RAY DIFFRACTION99.63
5.67-7.140.26131430.22872803X-RAY DIFFRACTION97.81
7.14-38.70.25441330.19662825X-RAY DIFFRACTION97.24
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.425305329651.21763860480.2463815815973.459808664670.2419305034052.09047395167-0.02454022316130.446357033972-0.373170775212-0.591840849049-0.0576017276235-0.3210328457190.3403835269810.07378158893510.07486097415850.6890075394090.1425095067540.1534607580780.677219160499-0.1397016325860.67782383879942.7778254148-23.6904678344-71.5911674686
21.795088504881.073032220320.4468757481612.690864527970.3904344294882.936574790920.12637013140.184417997658-0.01310675362270.187426315655-0.0304961840381-0.141962519434-0.1121188178670.421269406314-0.06031326844350.4598001354850.0462696787629-0.1025351850370.544684538834-0.03080415668280.45226233482558.0234312791-11.1076800603-9.76331139934
32.38891684936-0.0319232551968-0.3135540772732.29761198871-0.3458784506241.35026516817-0.06806968539510.08026662959860.1711245411440.2628062804670.03733575908210.0735157403983-0.205790354042-0.01068001663510.03698081996010.53583062327-0.006411676703-0.01839655383420.4307602302530.05115961480990.4307115995827.01449119353.1075821513-48.9387360834
46.305739939730.2758481020240.8215470850267.67064210547-1.83566461666.07774883787-0.2706040290850.7345968529041.094551073710.0596629550338-0.536353656029-1.5494519552-1.207918043440.7939857557090.8342054960120.848876627133-0.0848449113696-0.1374909693730.7675899246450.2973684931260.90370050754428.717422832724.248847956-93.8306386015
53.27389145652-2.083410387521.842555511776.94447702429-2.762736834624.849290076050.306775307891-0.0342986737396-0.162534638577-0.9535708318650.1609534000080.3858879317540.244078965502-0.541875102295-0.4790087466850.625806135924-0.0220173607741-0.06228826442320.5760930154020.06204565549990.61907393642619.6424147332.97006317683-72.8584777878
66.95999495068-1.47716012596-1.378749945114.671959251421.871573384841.60028915882-0.263045390989-0.2662114209580.0859235526522-0.2470826846720.1110389139810.196834742602-0.0258012542250.1029365333580.1177825587650.7616576450150.0469645267823-0.156430512210.4581645962560.1011706347350.4241130456952.8046082942222.7988329205-88.3752515934
71.677678201642.87395757691-2.119992243857.41679499394-3.200020105662.788203656050.7694389414910.8190299102341.4007454726-0.5351273144170.5021742912420.533472388743-0.184971018223-0.592388851585-1.090224655421.25075272995-0.0908781071490.08641413400420.8600388051740.1684869892841.02166405063.826178298638.7750388654-98.5063025955
83.279402197441.34801941157-3.096890857548.153283237222.896973130915.212798439081.185606299050.1283534986460.9498026754740.3063236181490.946244502733-0.459359887406-1.169478634440.267147052729-1.955782155940.959168309773-0.2582223878110.216302666011.01867743613-0.003288974613550.851178408856.3937059950643.2725944457-91.6322281241
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 11 through 355 )
2X-RAY DIFFRACTION2chain 'A' and (resid 394 through 672 )
3X-RAY DIFFRACTION3chain 'A' and (resid 713 through 1081 )
4X-RAY DIFFRACTION4chain 'C' and (resid 60 through 186)
5X-RAY DIFFRACTION5chain 'C' and (resid 200 through 317 )
6X-RAY DIFFRACTION6chain 'C' and (resid 319 through 427)
7X-RAY DIFFRACTION7chain 'E' and (resid 408 through 421 )
8X-RAY DIFFRACTION8chain 'E' and (resid 422 through 432 )

+
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