[English] 日本語
Yorodumi
- PDB-7k27: Crystal structure of the tandem bromodomain (BD1, BD2) of human T... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7k27
TitleCrystal structure of the tandem bromodomain (BD1, BD2) of human TAF1 bound to ATR inhibitor AZ20
ComponentsTranscription initiation factor TFIID subunit 1
KeywordsGENE REGULATION / Bromodomain / TAF1 / non-BET / BET / kinase inhibitor / ATR / dual BRD-kinase / transferase
Function / homology
Function and homology information


negative regulation of protein autoubiquitination / RNA polymerase I general transcription initiation factor activity / regulation of cell cycle G1/S phase transition / positive regulation of androgen receptor activity / RNA polymerase II general transcription initiation factor binding / cellular response to ATP / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / transcription regulator inhibitor activity / midbrain development ...negative regulation of protein autoubiquitination / RNA polymerase I general transcription initiation factor activity / regulation of cell cycle G1/S phase transition / positive regulation of androgen receptor activity / RNA polymerase II general transcription initiation factor binding / cellular response to ATP / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / transcription regulator inhibitor activity / midbrain development / histone acetyltransferase activity / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / ubiquitin conjugating enzyme activity / transcription initiation at RNA polymerase I promoter / MLL1 complex / negative regulation of ubiquitin-dependent protein catabolic process / positive regulation of transcription initiation by RNA polymerase II / RNA polymerase II core promoter sequence-specific DNA binding / histone H4K16 acetyltransferase activity / histone H3K56 acetyltransferase activity / histone H3K23 acetyltransferase activity / histone H2AK5 acetyltransferase activity / histone H2AK9 acetyltransferase activity / histone H2BK5 acetyltransferase activity / histone H2BK12 acetyltransferase activity / histone H3K4 acetyltransferase activity / histone H3K27 acetyltransferase activity / histone H3K36 acetyltransferase activity / histone H3K122 acetyltransferase activity / histone H3K18 acetyltransferase activity / histone H3K9 acetyltransferase activity / histone H3K14 acetyltransferase activity / histone H4K5 acetyltransferase activity / histone H4K8 acetyltransferase activity / histone H4K12 acetyltransferase activity / RNA polymerase II preinitiation complex assembly / histone acetyltransferase / RNA Polymerase II Pre-transcription Events / TBP-class protein binding / regulation of signal transduction by p53 class mediator / nuclear receptor binding / transcription initiation at RNA polymerase II promoter / peptidyl-threonine phosphorylation / lysine-acetylated histone binding / mRNA transcription by RNA polymerase II / protein polyubiquitination / cellular response to UV / p53 binding / kinase activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein binding / peptidyl-serine phosphorylation / ubiquitin-dependent protein catabolic process / protein autophosphorylation / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / sequence-specific DNA binding / transcription by RNA polymerase II / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / protein kinase activity / protein stabilization / protein phosphorylation / protein heterodimerization activity / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / chromatin / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / nucleus
Similarity search - Function
TAFII-230 TBP-binding / Transcription initiation factor TFIID subunit 1, animal / TAFII-230 TBP-binding domain superfamily / TATA box-binding protein binding / Zinc knuckle / Zinc knuckle / Transcription initiation factor TFIID subunit 1, histone acetyltransferase domain / Transcription initiation factor TFIID subunit 1 / Protein of unknown function (DUF3591) / Bromodomain, conserved site ...TAFII-230 TBP-binding / Transcription initiation factor TFIID subunit 1, animal / TAFII-230 TBP-binding domain superfamily / TATA box-binding protein binding / Zinc knuckle / Zinc knuckle / Transcription initiation factor TFIID subunit 1, histone acetyltransferase domain / Transcription initiation factor TFIID subunit 1 / Protein of unknown function (DUF3591) / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-VCD / Transcription initiation factor TFIID subunit 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsKarim, M.R. / Schonbrunn, E.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of Dual TAF1-ATR Inhibitors and Ligand-Induced Structural Changes of the TAF1 Tandem Bromodomain.
Authors: Karim, R.M. / Yang, L. / Chen, L. / Bikowitz, M.J. / Lu, J. / Grassie, D. / Shultz, Z.P. / Lopchuk, J.M. / Chen, J. / Schonbrunn, E.
History
DepositionSep 8, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 22, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 9, 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 23, 2022Group: 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 1.3Oct 18, 2023Group: 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: Transcription initiation factor TFIID subunit 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,7998
Polymers30,9681
Non-polymers8317
Water4,612256
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)45.260, 54.590, 123.420
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Transcription initiation factor TFIID subunit 1 / Cell cycle gene 1 protein / TBP-associated factor 250 kDa / p250 / Transcription initiation factor ...Cell cycle gene 1 protein / TBP-associated factor 250 kDa / p250 / Transcription initiation factor TFIID 250 kDa subunit / TAFII250


Mass: 30968.256 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TAF1, BA2R, CCG1, CCGS, TAF2A / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P21675, histone acetyltransferase, non-specific serine/threonine protein kinase

-
Non-polymers , 5 types, 263 molecules

#2: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical ChemComp-VCD / 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole


Mass: 412.505 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H24N4O3S / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 256 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.46 Å3/Da / Density % sol: 50.03 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.2 M Magnesium chloride hexahydrate, 0.1 M BIS-TRIS pH 5.5, 25% w/v Polyethylene glycol 3,350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 14, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.5→34.84 Å / Num. obs: 49801 / % possible obs: 99.9 % / Redundancy: 6.529 % / Biso Wilson estimate: 28.298 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.044 / Rrim(I) all: 0.048 / Χ2: 1.048 / Net I/σ(I): 21.77 / Num. measured all: 325145 / Scaling rejects: 3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.5-1.546.7310.6293.3324412363136270.8840.68199.9
1.54-1.586.630.5074.1423536355535500.9190.5599.9
1.58-1.636.4730.4085.0522307345634460.9530.44399.7
1.63-1.686.0870.3226.120373335133470.9680.35399.9
1.68-1.736.5120.2677.821221326232590.9780.2999.9
1.73-1.796.930.2199.9921553311431100.9870.23699.9
1.79-1.866.9220.17612.121106305030490.9910.19100
1.86-1.946.8450.13215.5920043293029280.9940.14399.9
1.94-2.026.7540.10119.7219148283628350.9960.109100
2.02-2.126.6420.07824.1717814268326820.9970.085100
2.12-2.246.360.06129.0116357257625720.9970.06699.8
2.24-2.375.8380.053214308245324510.9980.05599.9
2.37-2.546.6930.04636.9315360229522950.9980.05100
2.54-2.746.8240.04141.5514734215921590.9990.044100
2.74-36.670.03645.8913166197419740.9990.039100
3-3.356.450.03249.2811622180318020.9990.03599.9
3.35-3.876.140.02953.139885161316100.9990.03299.8
3.87-4.745.5010.02552.357531137913690.9990.02899.3
4.74-6.716.3660.02655.46926108810880.9990.028100
6.71-34.845.7760.02454.7237436526480.9990.02699.4

-
Processing

Software
NameVersionClassification
PHENIX1.18.2-3874_3874refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ID 7K03

7k03


Resolution: 1.5→34.84 Å / SU ML: 0.12 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 17.14 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1753 1245 2.5 %
Rwork0.1597 48553 -
obs0.1601 49798 99.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 88.16 Å2 / Biso mean: 28.7846 Å2 / Biso min: 13.63 Å2
Refinement stepCycle: final / Resolution: 1.5→34.84 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2018 0 117 256 2391
Biso mean--32.46 34.59 -
Num. residues----247
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 9 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
1.5-1.560.18681370.181753315468
1.56-1.630.21741350.174652735408
1.63-1.720.20681370.162453315468
1.72-1.820.17931380.15853745512
1.82-1.970.18291370.158453395476
1.97-2.160.17551380.147353785516
2.16-2.480.15621380.146353885526
2.48-3.120.16751400.162954575597
3.12-34.840.17641450.163756825827
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)
11.63770.4144-0.93031.2153-0.21852.68390.028-0.14350.08860.18-0.01620.01090.0337-0.0987-0.02620.1408-0.00470.00040.1173-0.00820.1304-128.1294-153.0421134.8811
21.66390.4292-1.03831.4221-0.23342.80340.0157-0.0545-0.19110.0672-0.0992-0.02950.0384-0.00010.08430.1301-0.0029-0.01720.1465-0.01150.1865-137.1418-175.4521127.8321
35.9194-2.3643-1.59632.21373.39296.6045-0.1667-0.2384-0.1590.3467-0.00460.03340.451-0.48070.18830.3778-0.06610.02160.30270.05990.1751-147.3952-177.2135147.6288
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 1380 through 1501 )A0
2X-RAY DIFFRACTION2chain 'A' and (resid 1502 through 1606 )A0
3X-RAY DIFFRACTION3chain 'A' and (resid 1607 through 1626 )A0

+
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