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Basic information

Entry
Database: PDB / ID: 2axl
TitleSolution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein
ComponentsWerner syndrome
KeywordsDNA BINDING PROTEIN / PROTEIN BINDING / the WH-like domain
Function / homology
Function and homology information


3'-flap-structured DNA binding / positive regulation of strand invasion / forked DNA-dependent helicase activity / 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 / G-quadruplex DNA unwinding ...3'-flap-structured DNA binding / positive regulation of strand invasion / forked DNA-dependent helicase activity / 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 / G-quadruplex DNA unwinding / t-circle formation / telomeric D-loop disassembly / Y-form DNA binding / four-way junction helicase activity / G-quadruplex DNA binding / MutLalpha complex binding / bubble DNA binding / Processive synthesis on the C-strand of the telomere / Impaired BRCA2 binding to PALB2 / Removal of the Flap Intermediate from the C-strand / protein localization to nucleolus / DNA 3'-5' helicase / 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) / response to UV-C / Resolution of D-loop Structures through Holliday Junction Intermediates / exonuclease activity / DNA metabolic process / DNA duplex unwinding / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / 3'-5' DNA helicase activity / DNA synthesis involved in DNA repair / DNA unwinding involved in DNA replication / replication fork processing / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / SUMOylation of DNA damage response and repair proteins / four-way junction DNA binding / 3'-5' exonuclease activity / DNA helicase activity / telomere maintenance / cellular response to starvation / replication fork / isomerase activity / determination of adult lifespan / double-strand break repair via homologous recombination / base-excision repair / G2/M DNA damage checkpoint / HDR through Homologous Recombination (HRR) / cellular response to gamma radiation / 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 / DNA replication / chromosome, telomeric region / Hydrolases; Acting on ester bonds / 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 / ATP-dependent DNA helicase RecQ, zinc-binding domain / RecQ zinc-binding / DNA helicase, ATP-dependent, RecQ type / Helicase and RNase D C-terminal / HRDC domain ...Helicase Helix-turn-helix domain / Helix-turn-helix domain / RQC domain / RQC / RQC domain / ATP-dependent DNA helicase RecQ, zinc-binding domain / RecQ zinc-binding / DNA helicase, ATP-dependent, RecQ type / Helicase and RNase D C-terminal / HRDC domain / HRDC domain / HRDC domain profile. / 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 / Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain / 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 / Arc Repressor Mutant, subunit A / 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 / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing torsion angle dynamics
AuthorsHu, J.-S. / Feng, H. / Zeng, W. / Lin, G.-X. / Xi, X.G.
CitationJournal: Proc.Natl.Acad.Sci.Usa / Year: 2005
Title: Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein.
Authors: Hu, J.-S. / Feng, H. / Zeng, W. / Lin, G.-X. / Xi, X.G.
History
DepositionSep 5, 2005Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 13, 2005Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Mar 9, 2022Group: Database references / Derived calculations
Category: database_2 / pdbx_struct_assembly / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4May 22, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Werner syndrome


Theoretical massNumber of molelcules
Total (without water)16,4291
Polymers16,4291
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)10 / 40back calculated data agree with experimental NOESY spectrum,structures with acceptable covalent geometry
RepresentativeModel #1fewest violations

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Components

#1: Protein Werner syndrome


Mass: 16428.713 Da / Num. of mol.: 1 / Fragment: The DPBD
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: pET32d / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: Q14191

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
111D 15N-separated NOESY
1213D 15N-separated NOESY
1314D 13C-separated NOESY
1414D 13C/15N-separated NOESY
151HNHA
161HNCG arom, HN(CO)CG arom
NMR detailsText: HCCH-COSY was optimized for detection for CH3 groups, 2D spin echo for 1H-13C HSQC selected for aromatic and Carbonyl containing residues

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Sample preparation

DetailsContents: 0.35 mM in KPi buffer (pH7.4) 25 mM NaCl / Solvent system: 92.5% H2O/7.5% D2O
Sample conditionsIonic strength: 25 mM KPi + 25 mM NaCl / pH: 7.4 / Pressure: 1 atm / Temperature: 295.2 K

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NMR measurement

RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M
Radiation wavelengthRelative weight: 1
NMR spectrometerType: Bruker DRX / Manufacturer: Bruker / Model: DRX / Field strength: 600 MHz

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Processing

NMR software
NameVersionDeveloperClassification
xplor-nihXPLOR-NIHSchwieters, C.D., Kuszewski, J., Tjandra, N. & Clore, G.M. (2003)structure solution
xplor-nihXPLOR-NIHSchwieters, C.D., Kuszewski, J., Tjandra, N. & Clore, G.M. (2003)refinement
RefinementMethod: simulated annealing torsion angle dynamics / Software ordinal: 1
NMR representativeSelection criteria: fewest violations
NMR ensembleConformer selection criteria: back calculated data agree with experimental NOESY spectrum,structures with acceptable covalent geometry
Conformers calculated total number: 40 / Conformers submitted total number: 10

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