[English] 日本語
Yorodumi
- PDB-8br9: Stapled peptide SP24 in complex with humanised RadA mutant HumRadA22 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8br9
TitleStapled peptide SP24 in complex with humanised RadA mutant HumRadA22
Components
  • Breast cancer type 2 susceptibility protein
  • DNA repair and recombination protein RadA
KeywordsRECOMBINATION / Stapled peptide / Rad51 / BRCA2 / BRC repeat
Function / homology
Function and homology information


BRCA2-MAGE-D1 complex / negative regulation of mammary gland epithelial cell proliferation / establishment of protein localization to telomere / mitotic recombination-dependent replication fork processing / nuclear ubiquitin ligase complex / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / histone H4 acetyltransferase activity / histone H3 acetyltransferase activity / lateral element ...BRCA2-MAGE-D1 complex / negative regulation of mammary gland epithelial cell proliferation / establishment of protein localization to telomere / mitotic recombination-dependent replication fork processing / nuclear ubiquitin ligase complex / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / histone H4 acetyltransferase activity / histone H3 acetyltransferase activity / lateral element / regulation of DNA damage checkpoint / Impaired BRCA2 binding to PALB2 / telomere maintenance via recombination / gamma-tubulin binding / HDR through MMEJ (alt-NHEJ) / oocyte maturation / DNA repair complex / response to UV-C / inner cell mass cell proliferation / 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) / Resolution of D-loop Structures through Holliday Junction Intermediates / ATP-dependent DNA damage sensor activity / female gonad development / hematopoietic stem cell proliferation / Impaired BRCA2 binding to RAD51 / male meiosis I / centrosome duplication / Presynaptic phase of homologous DNA pairing and strand exchange / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / response to X-ray / positive regulation of mitotic cell cycle / secretory granule / regulation of cytokinesis / response to gamma radiation / cellular response to ionizing radiation / nucleotide-excision repair / DNA damage response, signal transduction by p53 class mediator / double-strand break repair via homologous recombination / brain development / HDR through Homologous Recombination (HRR) / Meiotic recombination / cellular senescence / double-strand break repair / single-stranded DNA binding / protease binding / spermatogenesis / DNA recombination / damaged DNA binding / chromosome, telomeric region / DNA repair / centrosome / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / protein-containing complex / ATP hydrolysis activity / nucleoplasm / ATP binding / identical protein binding / nucleus / cytosol
Similarity search - Function
BRCA2, OB3 / Tower domain / Breast cancer type 2 susceptibility protein, helical domain / BRCA2 helical domain superfamily / : / : / BRCA2, oligonucleotide/oligosaccharide-binding, domain 3 / Tower / BRCA2, helical / BRCA2, OB2 ...BRCA2, OB3 / Tower domain / Breast cancer type 2 susceptibility protein, helical domain / BRCA2 helical domain superfamily / : / : / BRCA2, oligonucleotide/oligosaccharide-binding, domain 3 / Tower / BRCA2, helical / BRCA2, OB2 / BRCA2 TR2 domain / Tower / BRCA2 repeat / BRCA2, OB1 / Breast cancer type 2 susceptibility protein / BRCA2 repeat / BRCA2, oligonucleotide/oligosaccharide-binding, domain 1 / BRCA2 repeat profile. / DNA recombination/repair protein RadA / DNA recombination and repair protein, RecA-like / DNA recombination and repair protein Rad51-like, C-terminal / Rad51 / DNA recombination and repair protein RecA, monomer-monomer interface / RecA family profile 2. / DNA recombination and repair protein RecA-like, ATP-binding domain / RecA family profile 1. / DNA repair Rad51/transcription factor NusA, alpha-helical / Helix-hairpin-helix domain / Helix-hairpin-helix DNA-binding motif, class 1 / Helix-hairpin-helix DNA-binding motif class 1 / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / 4,6-diethylpyrimidin-2-amine / DNA repair and recombination protein RadA / Breast cancer type 2 susceptibility protein
Similarity search - Component
Biological speciesPyrococcus furiosus (archaea)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.63 Å
AuthorsPantelejevs, T. / Hyvonen, M.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)DTP United Kingdom
Citation
Journal: Chem Sci / Year: 2023
Title: A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase.
Authors: Pantelejevs, T. / Zuazua-Villar, P. / Koczy, O. / Counsell, A.J. / Walsh, S.J. / Robertson, N.S. / Spring, D.R. / Downs, J.A. / Hyvonen, M.
#1: Journal: Biorxiv / Year: 2023
Title: A Recombinant Approach For Stapled Peptide Discovery Yields Inhibitors of the RAD51 Recombinase
Authors: Pantelejevs, T. / Zuazua-Villar, P. / Koczy, O. / Counsell, A. / Walsh, S.J. / Robertson, N.S. / Spring, D.R. / Downs, J. / Hyvonen, M.
History
DepositionNov 22, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 8, 2023Provider: repository / Type: Initial release
Revision 1.1Dec 27, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Revision 1.2Feb 7, 2024Group: Refinement description / Category: pdbx_initial_refinement_model
Item: _pdbx_initial_refinement_model.accession_code / _pdbx_initial_refinement_model.source_name
Revision 1.3Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: DNA repair and recombination protein RadA
B: Breast cancer type 2 susceptibility protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,1064
Polymers29,5282
Non-polymers5782
Water1,47782
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2290 Å2
ΔGint-20 kcal/mol
Surface area11250 Å2
MethodPISA
Unit cell
Length a, b, c (Å)140.464, 38.642, 43.528
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Space group name HallP22ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x+1/2,y+1/2,-z
#4: -x,-y,z
Components on special symmetry positions
IDModelComponents
11A-521-

HOH

-
Components

#1: Protein DNA repair and recombination protein RadA / Humanised RadA mutant HumRadA22


Mass: 25542.064 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Pyrococcus furiosus (archaea) / Gene: radA, PF1926 / Production host: Escherichia coli (E. coli) / References: UniProt: O74036
#2: Protein/peptide Breast cancer type 2 susceptibility protein / Fanconi anemia group D1 protein


Mass: 3985.500 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRCA2, FACD, FANCD1 / Production host: Escherichia coli (E. coli) / References: UniProt: P51587
#3: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM
#4: Chemical ChemComp-RF6 / 4,6-diethylpyrimidin-2-amine / 4,6-bis(ethenyl)pyrimidin-2-amine (precursor) / 4,6-Divinylpyrimidin-2-amine (precursor) / peptide staple


Mass: 151.209 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H13N3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 82 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46.53 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, sitting drop
Details: 0.1 M Na 3 Cit 4.2 pH (Buffer) 20 %w/v PEG 1K (Precipitant) 0.2 M Li 2 SO4 (Salt)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jan 19, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.63→70.23 Å / Num. obs: 30303 / % possible obs: 98.7 % / Redundancy: 7.9 % / Biso Wilson estimate: 39.72 Å2 / CC1/2: 1 / Rrim(I) all: 0.059 / Net I/σ(I): 12
Reflection shellResolution: 1.63→1.66 Å / Mean I/σ(I) obs: 0.3 / Num. unique obs: 11733 / CC1/2: 0.3

-
Processing

Software
NameVersionClassification
BUSTERrefinement
PHENIX1.19.2_4158refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6HQU

6hqu


Resolution: 1.63→43.53 Å / SU ML: 0.321 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 41.9146
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2816 1444 4.93 %
Rwork0.25 27833 -
obs0.2515 29277 95.41 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 62.1 Å2
Refinement stepCycle: LAST / Resolution: 1.63→43.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1854 0 38 82 1974
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01271925
X-RAY DIFFRACTIONf_angle_d1.60362592
X-RAY DIFFRACTIONf_chiral_restr0.1002290
X-RAY DIFFRACTIONf_plane_restr0.0058341
X-RAY DIFFRACTIONf_dihedral_angle_d15.1536727
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.63-1.690.51551160.54171980X-RAY DIFFRACTION69.27
1.69-1.750.48141630.47382729X-RAY DIFFRACTION96.08
1.75-1.830.50791470.4582792X-RAY DIFFRACTION97.64
1.83-1.930.37511250.37342838X-RAY DIFFRACTION97.72
1.93-2.050.3521370.29372830X-RAY DIFFRACTION98.15
2.05-2.210.3261460.29712832X-RAY DIFFRACTION98.32
2.21-2.430.29351660.27552873X-RAY DIFFRACTION98.16
2.43-2.780.3031410.26752900X-RAY DIFFRACTION99.35
2.78-3.50.27841630.24792936X-RAY DIFFRACTION99.49
3.5-43.530.23931400.21213123X-RAY DIFFRACTION99.36
Refinement TLS params.Method: refined / Origin x: 19.2704162755 Å / Origin y: -26.3070323133 Å / Origin z: 1.8340566476 Å
111213212223313233
T0.42616890283 Å2-0.0488729083112 Å2-0.0257259511287 Å2-0.308521290065 Å20.0142291589933 Å2--0.254209943153 Å2
L3.08112648419 °20.755830455827 °20.344779557802 °2-2.09394124151 °2-0.822674024317 °2--6.07610517046 °2
S-0.180404119604 Å °-0.139648616588 Å °-0.0458727849536 Å °-0.0171782837694 Å °-0.00290564937696 Å °-0.000650007875594 Å °-0.206260341813 Å °0.151575495579 Å °0.179819811271 Å °
Refinement TLS groupSelection details: {A|* B|*}

+
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