[English] 日本語
Yorodumi
- PDB-7q6u: Crystal structure of the bromodomain of ATAD2 with phenol HTS hit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7q6u
TitleCrystal structure of the bromodomain of ATAD2 with phenol HTS hit (cpd 6)
ComponentsATPase family AAA domain-containing protein 2
KeywordsGENE REGULATION / bromodomain / epigenetics
Function / homology
Function and homology information


nucleosome disassembly / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transcription initiation-coupled chromatin remodeling / nucleosome assembly / histone binding / chromatin binding / positive regulation of DNA-templated transcription / ATP hydrolysis activity / extracellular exosome ...nucleosome disassembly / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transcription initiation-coupled chromatin remodeling / nucleosome assembly / histone binding / chromatin binding / positive regulation of DNA-templated transcription / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / nucleus
Similarity search - Function
ATPase family AAA domain-containing protein ATAD2-like / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / Bromodomain / Bromodomain profile. / bromo domain ...ATPase family AAA domain-containing protein ATAD2-like / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Chem-963 / ATPase family AAA domain-containing protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsPatel, S.J. / Winter-Holt, J.J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models.
Authors: Winter-Holt, J.J. / Bardelle, C. / Chiarparin, E. / Dale, I.L. / Davey, P.R.J. / Davies, N.L. / Denz, C. / Fillery, S.M. / Guerot, C.M. / Han, F. / Hughes, S.J. / Kulkarni, M. / Liu, Z. / ...Authors: Winter-Holt, J.J. / Bardelle, C. / Chiarparin, E. / Dale, I.L. / Davey, P.R.J. / Davies, N.L. / Denz, C. / Fillery, S.M. / Guerot, C.M. / Han, F. / Hughes, S.J. / Kulkarni, M. / Liu, Z. / Milbradt, A. / Moss, T.A. / Niu, H. / Patel, J. / Rabow, A.A. / Schimpl, M. / Shi, J. / Sun, D. / Yang, D. / Guichard, S.
History
DepositionNov 9, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 19, 2022Provider: repository / Type: Initial release
Revision 1.1Feb 16, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Mar 9, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3May 1, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ATPase family AAA domain-containing protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,1105
Polymers15,4541
Non-polymers6574
Water3,459192
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area480 Å2
ΔGint-33 kcal/mol
Surface area7990 Å2
MethodPISA
Unit cell
Length a, b, c (Å)79.039, 79.039, 137.850
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Components on special symmetry positions
IDModelComponents
11A-1203-

SO4

21A-1406-

HOH

-
Components

#1: Protein ATPase family AAA domain-containing protein 2 / AAA nuclear coregulator cancer-associated protein / ANCCA


Mass: 15453.514 Da / Num. of mol.: 1 / Fragment: bromodomain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ATAD2, L16, PRO2000 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): Gold / References: UniProt: Q6PL18, adenosinetriphosphatase
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-963 / (1R,9S)-13-(3,5-dimethoxy-4-oxidanyl-phenyl)carbonyl-11,13-diazatricyclo[7.3.1.0^{2,7}]trideca-2,4,6-trien-10-one


Mass: 368.383 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20N2O5 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 192 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.02 Å3/Da / Density % sol: 69.42 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 6.25
Details: ATAD2 (981-1108) at 12 mg/ml in 25 mM Tris pH 9.7, 300 mM NaCl, 0.5 mM TCEP crystallised from 20% PEG 3350, 0.2 M ammonium sulfate, 0.1 M Bis-Tris pH 6.25. Ligands were introduced by ...Details: ATAD2 (981-1108) at 12 mg/ml in 25 mM Tris pH 9.7, 300 mM NaCl, 0.5 mM TCEP crystallised from 20% PEG 3350, 0.2 M ammonium sulfate, 0.1 M Bis-Tris pH 6.25. Ligands were introduced by soaking, cryo-protection with 20 % glycerol.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ / Wavelength: 1.5406 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: Jul 7, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5406 Å / Relative weight: 1
ReflectionResolution: 1.95→68.93 Å / Num. obs: 19205 / % possible obs: 99.8 % / Redundancy: 5.8 % / Biso Wilson estimate: 26.76 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.095 / Rpim(I) all: 0.042 / Rrim(I) all: 0.104 / Net I/σ(I): 17 / Num. measured all: 112343
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.95-2.115.30.6672029238320.7470.3080.7382.999.1
5.17-68.935.40.0266417119810.0120.02950.599.5

-
Processing

Software
NameVersionClassification
Aimless0.2.17data scaling
BUSTER2.11.5refinement
PDB_EXTRACT3.27data extraction
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: internal model

Resolution: 1.95→48.57 Å / Cor.coef. Fo:Fc: 0.9431 / Cor.coef. Fo:Fc free: 0.9424 / SU R Cruickshank DPI: 0.112 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.127 / SU Rfree Blow DPI: 0.111 / SU Rfree Cruickshank DPI: 0.102
RfactorNum. reflection% reflectionSelection details
Rfree0.1993 973 5.08 %RANDOM
Rwork0.1858 ---
obs0.1865 19140 99.32 %-
Displacement parametersBiso max: 99.7 Å2 / Biso mean: 31.25 Å2 / Biso min: 11.51 Å2
Baniso -1Baniso -2Baniso -3
1-0.1181 Å20 Å20 Å2
2--0.1181 Å20 Å2
3----0.2361 Å2
Refine analyzeLuzzati coordinate error obs: 0.204 Å
Refinement stepCycle: final / Resolution: 1.95→48.57 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1084 0 42 192 1318
Biso mean--45.37 44.36 -
Num. residues----130
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d439SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes36HARMONIC2
X-RAY DIFFRACTIONt_gen_planes167HARMONIC5
X-RAY DIFFRACTIONt_it1163HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion153SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact1528SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d1163HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg1584HARMONIC20.88
X-RAY DIFFRACTIONt_omega_torsion2.61
X-RAY DIFFRACTIONt_other_torsion16.62
LS refinement shellResolution: 1.95→2.06 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.2259 136 5.18 %
Rwork0.2279 2490 -
all0.2278 2626 -
obs--99.32 %

+
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