[English] 日本語
Yorodumi
- PDB-9og3: Crystal structure of WRN in complex with compound 4 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9og3
TitleCrystal structure of WRN in complex with compound 4
ComponentsBifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
KeywordsHYDROLASE / Werner syndrome helicase
Function / homology
Function and homology information


3'-flap-structured DNA binding / positive regulation of strand invasion / telomeric G-quadruplex DNA binding / positive regulation of hydrolase activity / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / regulation of growth rate / telomere maintenance via semi-conservative replication / t-circle formation / telomeric D-loop disassembly ...3'-flap-structured DNA binding / positive regulation of strand invasion / telomeric G-quadruplex DNA binding / positive regulation of hydrolase activity / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / regulation of growth rate / telomere maintenance via semi-conservative replication / t-circle formation / telomeric D-loop disassembly / DNA geometric change / Y-form DNA binding / G-quadruplex DNA binding / bubble DNA binding / MutLalpha complex binding / Impaired BRCA2 binding to PALB2 / Processive synthesis on the C-strand of the telomere / protein localization to nucleolus / Removal of the Flap Intermediate from the C-strand / response to UV-C / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / exonuclease activity / 3'-5' DNA helicase activity / Resolution of D-loop Structures through Holliday Junction Intermediates / DNA 3'-5' helicase / HDR through Single Strand Annealing (SSA) / DNA metabolic process / Impaired BRCA2 binding to RAD51 / DNA synthesis involved in DNA repair / replication fork processing / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / SUMOylation of DNA damage response and repair proteins / DNA helicase activity / four-way junction DNA binding / 3'-5' exonuclease activity / telomere maintenance / cellular response to starvation / replication fork / determination of adult lifespan / isomerase activity / double-strand break repair via homologous recombination / G2/M DNA damage checkpoint / cellular response to gamma radiation / base-excision repair / HDR through Homologous Recombination (HRR) / cellular senescence / double-strand break repair / manganese ion binding / chromosome / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / response to oxidative stress / Hydrolases; Acting on ester bonds / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / chromosome, telomeric region / DNA replication / nuclear speck / centrosome / DNA damage response / chromatin binding / protein-containing complex binding / nucleolus / magnesium ion binding / protein homodimerization activity / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / nucleus / cytoplasm
Similarity search - Function
Helicase Helix-turn-helix domain / Helix-turn-helix domain / RQC domain / RQC / RQC domain / Helicase and RNase D C-terminal / HRDC domain / HRDC domain / HRDC domain profile. / ATP-dependent DNA helicase RecQ, zinc-binding domain ...Helicase Helix-turn-helix domain / Helix-turn-helix domain / RQC domain / RQC / RQC domain / Helicase and RNase D C-terminal / HRDC domain / HRDC domain / HRDC domain profile. / ATP-dependent DNA helicase RecQ, zinc-binding domain / RecQ zinc-binding / DNA helicase, ATP-dependent, RecQ type / HRDC domain superfamily / 3'-5' exonuclease / 3'-5' exonuclease / 3'-5' exonuclease domain / HRDC-like superfamily / DEAD/DEAH box helicase domain / DEAD/DEAH box helicase / Helicase conserved C-terminal domain / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Ribonuclease H superfamily / Ribonuclease H-like superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
: / Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.06 Å
AuthorsPemberton, O.A. / Tong, Y. / Nocek, B. / Tang, H.Y.H.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2025
Title: Validation, Key Pharmacophores, and X-ray Cocrystal Structures of Novel Biochemically and Cellularly Active WRN Inhibitors Derived from a DNA-Encoded Library Screen.
Authors: Tong, Y. / Baker, K.A. / Chapman, A.M. / Elsen, N.L. / Fowler, F. / George, M.D. / Gesmundo, N.J. / Hatton, H. / Hickey, M. / Hutchins, C.W. / Jeffries, C.L. / Kelly, A. / Korepanova, A. / ...Authors: Tong, Y. / Baker, K.A. / Chapman, A.M. / Elsen, N.L. / Fowler, F. / George, M.D. / Gesmundo, N.J. / Hatton, H. / Hickey, M. / Hutchins, C.W. / Jeffries, C.L. / Kelly, A. / Korepanova, A. / Miller, I.R. / Nocek, B. / Panchal, S.C. / Pemberton, O.A. / Qiu, W. / Talaty, N.N. / Hin Tang, H.Y. / Towne, D. / Zhang, M. / Zhao, Y. / Gopalakrishnan, S.M. / Sun, C. / Kort, M.E. / Dart, M.J. / Firestone, A.J.
History
DepositionApr 30, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 18, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,9623
Polymers48,2341
Non-polymers7282
Water2,792155
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)65.370, 68.717, 108.069
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN / DNA helicase / RecQ-like type 3 / RecQ protein-like 2 / Werner syndrome protein


Mass: 48233.812 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WRN, RECQ3, RECQL2 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q14191, Hydrolases; Acting on ester bonds, DNA 3'-5' helicase
#2: Chemical ChemComp-A1CA4 / (3R,4S)-N-[(2R)-3-cyclohexyl-1-(dimethylamino)-1-oxopropan-2-yl]-1-[(2-fluoro-4-methylphenyl)acetyl]-4-[3-(2-oxo-2,3-dihydro-1H-1,3-benzimidazol-1-yl)propanamido]piperidine-3-carboxamide


Mass: 662.794 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C36H47FN6O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 155 / 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: 2.52 Å3/Da / Density % sol: 51.12 %
Crystal growTemperature: 290.15 K / Method: vapor diffusion, hanging drop / Details: 18% w/v PEG3350 and 0.18 M Tri-sodium citrate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Dec 9, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.06→57.99 Å / Num. obs: 29296 / % possible obs: 94.6 % / Redundancy: 6.6 % / CC1/2: 0.994 / Rmerge(I) obs: 0.21 / Rpim(I) all: 0.088 / Rrim(I) all: 0.228 / Χ2: 0.89 / Net I/σ(I): 6.6 / Num. measured all: 193274
Reflection shellResolution: 2.06→2.17 Å / % possible obs: 87.4 % / Redundancy: 6.4 % / Rmerge(I) obs: 2.141 / Num. measured all: 24910 / Num. unique obs: 3887 / CC1/2: 0.389 / Rpim(I) all: 0.902 / Rrim(I) all: 2.328 / Χ2: 0.82 / Net I/σ(I) obs: 0.9

-
Processing

Software
NameVersionClassification
PHENIX1.21.2_5419refinement
Aimless0.7.15data scaling
autoPROC1.1.7data reduction
PHASER2.8.3phasing
PDB_EXTRACT4.3data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.06→55.93 Å / SU ML: 0.33 / Cross valid method: FREE R-VALUE / σ(F): 1.9 / Phase error: 28.82 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2584 2615 4.84 %
Rwork0.2235 --
obs0.2251 28866 92.76 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.06→55.93 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3317 0 49 155 3521
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0023436
X-RAY DIFFRACTIONf_angle_d0.4774639
X-RAY DIFFRACTIONf_dihedral_angle_d15.491322
X-RAY DIFFRACTIONf_chiral_restr0.042509
X-RAY DIFFRACTIONf_plane_restr0.005604
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.06-2.10.3596720.38121344X-RAY DIFFRACTION46
2.1-2.140.4041510.33892802X-RAY DIFFRACTION97
2.14-2.180.37791410.33542906X-RAY DIFFRACTION98
2.18-2.230.36261680.32792794X-RAY DIFFRACTION98
2.23-2.280.35011190.32271984X-RAY DIFFRACTION69
2.28-2.340.31421290.29612939X-RAY DIFFRACTION100
2.34-2.40.31171230.29722938X-RAY DIFFRACTION100
2.4-2.470.29521390.282928X-RAY DIFFRACTION100
2.47-2.550.27761530.26742893X-RAY DIFFRACTION100
2.55-2.640.33961440.26162954X-RAY DIFFRACTION100
2.64-2.750.33631190.26552237X-RAY DIFFRACTION77
2.75-2.870.29661420.24872947X-RAY DIFFRACTION100
2.87-3.020.30191640.242864X-RAY DIFFRACTION100
3.02-3.210.25921450.22752935X-RAY DIFFRACTION100
3.21-3.460.2541380.21622676X-RAY DIFFRACTION92
3.46-3.810.21381300.17962711X-RAY DIFFRACTION92
3.81-4.360.17491590.16712782X-RAY DIFFRACTION95
4.36-5.490.19111300.15882917X-RAY DIFFRACTION100
5.49-55.930.22431490.1872905X-RAY DIFFRACTION100

+
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