[English] 日本語
Yorodumi
- PDB-7k6h: Crystal structure of the first bromodomain (BD1) of human BRD4 bo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7k6h
TitleCrystal structure of the first bromodomain (BD1) of human BRD4 bound to XMD8-92
ComponentsBromodomain-containing protein 4
KeywordsGENE REGULATION / BET / ERK5 / dual BRD-kinase inhibitor
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of T-helper 17 cell lineage commitment / : / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome ...RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of T-helper 17 cell lineage commitment / : / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / transcription coregulator activity / positive regulation of transcription elongation by RNA polymerase II / p53 binding / chromosome / regulation of inflammatory response / histone binding / Potential therapeutics for SARS / transcription coactivator activity / positive regulation of canonical NF-kappaB signal transduction / transcription cis-regulatory region binding / chromatin remodeling / protein serine/threonine kinase activity / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / chromatin / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus
Similarity search - Function
Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site ...Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-4WG / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsKarim, M.R. / Zhu, J.Y. / Schonbrunn, E.
CitationJournal: J.Med.Chem. / Year: 2021
Title: Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.
Authors: Karim, R.M. / Bikowitz, M.J. / Chan, A. / Zhu, J.Y. / Grassie, D. / Becker, A. / Berndt, N. / Gunawan, S. / Lawrence, N.J. / Schonbrunn, E.
History
DepositionSep 20, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 22, 2021Provider: repository / Type: Initial release
Revision 1.1Nov 17, 2021Group: 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 1.2Nov 24, 2021Group: 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: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,5742
Polymers15,0991
Non-polymers4751
Water2,216123
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area7790 Å2
MethodPISA
Unit cell
Length a, b, c (Å)41.820, 52.030, 57.270
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Bromodomain-containing protein 4 / Protein HUNK1


Mass: 15099.380 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885
#2: Chemical ChemComp-4WG / 2-{[2-ethoxy-4-(4-hydroxypiperidin-1-yl)phenyl]amino}-5,11-dimethyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one


Mass: 474.555 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H30N6O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 123 / 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: 2.06 Å3/Da / Density % sol: 40.38 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.2 M Ammonium acetate, 0.1 M Sodium citrate tribasic dihydrate pH 5.6, 30% w/v Polyethylene glycol 4,000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Apr 5, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.5→28.635 Å / Num. obs: 20618 / % possible obs: 99.9 % / Redundancy: 6.999 % / Biso Wilson estimate: 16.68 Å2 / CC1/2: 0.991 / Rmerge(I) obs: 0.107 / Rrim(I) all: 0.116 / Χ2: 0.985 / Net I/σ(I): 18.6 / Num. measured all: 144304
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
1.5-1.547.0590.09615.6310695151515150.9920.104100
1.54-1.587.0480.09116.0110184144514450.9910.098100
1.58-1.637.0480.0916.6510001142014190.9920.09799.9
1.63-1.687.080.08617.569898139813980.9920.093100
1.68-1.737.0810.08317.929397132713270.9930.089100
1.73-1.797.0620.08418.29216130513050.9920.091100
1.79-1.867.0970.08418.948935125912590.9930.091100
1.86-1.947.0990.08319.368576120812080.990.089100
1.94-2.027.1380.0819.758259115711570.9930.086100
2.02-2.127.0760.08219.857826110711060.9930.08999.9
2.12-2.247.0850.08420.17588107210710.990.09199.9
2.24-2.377.0670.09519.997166101510140.9860.10399.9
2.37-2.547.040.120.2166889509500.9850.109100
2.54-2.746.9490.11320.0762829049040.9860.122100
2.74-36.8830.11720.0256308208180.9850.12799.8
3-3.356.8410.11720.0150907447440.9840.126100
3.35-3.876.7520.11319.9445176696690.9820.122100
3.87-4.746.7160.11119.8739295855850.9830.12100
4.74-6.716.4630.11519.4229154524510.9840.12599.8
6.71-28.6355.5380.10917.7715122772730.9780.11998.6

-
Processing

Software
NameVersionClassification
PHENIX1.12-2829_2829refinement
XSCALEdata scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7K6G

7k6g


Resolution: 1.5→28.635 Å / SU ML: 0.11 / Cross valid method: THROUGHOUT / σ(F): 1.4 / Phase error: 18.8 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1903 1031 5 %
Rwork0.1649 19582 -
obs0.1662 20613 99.96 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 145.86 Å2 / Biso mean: 29.6633 Å2 / Biso min: 10.2 Å2
Refinement stepCycle: final / Resolution: 1.5→28.635 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1059 0 65 123 1247
Biso mean--28.92 38.14 -
Num. residues----127
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0061171
X-RAY DIFFRACTIONf_angle_d0.8711603
X-RAY DIFFRACTIONf_chiral_restr0.041165
X-RAY DIFFRACTIONf_plane_restr0.005207
X-RAY DIFFRACTIONf_dihedral_angle_d17.673724
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork
1.5-1.57910.22761450.1772754
1.5791-1.6780.20751450.16822757
1.678-1.80760.22191440.17522745
1.8076-1.98950.18561470.16642777
1.9895-2.27720.17411460.15392786
2.2772-2.86860.17641480.17262812
2.8686-28.6350.19281560.16122951
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)
12.24051.61561.58962.18092.03481.9913-0.00480.5526-0.0935-0.2304-0.14710.2847-0.4002-0.4260.10960.29660.09860.01450.22680.05930.2016-18.316111.4003-23.1907
25.8846-2.36095.26491.5221-2.35394.8910.03520.50230.0192-0.1974-0.107-0.04260.19530.47840.07890.1242-0.01290.01790.127-0.00340.18311.54610.8417-25.6351
33.8078-1.4612-5.71743.64613.12778.8529-0.3551-0.7315-0.44320.21610.12270.14810.71090.42970.15840.16550.03050.02430.15310.02970.2-3.1740.908-10.5939
48.114-4.13262.93112.4574-0.92532.0505-0.1518-0.8584-0.19460.51930.30080.1342-0.084-0.2911-0.11640.1830.00140.03250.17290.02780.1511-10.47285.7535-4.6808
53.9873-4.7277-0.05365.9364-0.11471.9118-0.3573-0.7324-0.34540.61730.56750.8309-0.2902-0.93-0.12450.18930.09870.06220.35480.02580.2341-21.323413.6465-11.9328
64.5935-3.733-2.77254.22123.55584.66870.06120.11570.0449-0.1922-0.09120.0442-0.2292-0.17840.04230.0987-0.0019-0.01250.09910.01190.1157-9.0419.9969-20.8482
76.7478-6.1001-6.94295.57786.51617.75020.2289-0.01390.2367-0.27630.0618-0.3544-0.27440.1127-0.31430.1191-0.01430.00070.1-0.00280.1664-4.15214.817-15.5127
85.7488-4.4919-5.6755.89724.57127.9265-0.0247-0.38140.18440.07660.2703-0.46410.17180.4647-0.10520.1267-0.0286-0.02250.1184-0.00310.1806-0.301911.001-8.0287
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 42 through 51 )A42 - 51
2X-RAY DIFFRACTION2chain 'A' and (resid 52 through 68 )A52 - 68
3X-RAY DIFFRACTION3chain 'A' and (resid 69 through 76 )A69 - 76
4X-RAY DIFFRACTION4chain 'A' and (resid 77 through 83 )A77 - 83
5X-RAY DIFFRACTION5chain 'A' and (resid 84 through 96 )A84 - 96
6X-RAY DIFFRACTION6chain 'A' and (resid 97 through 121 )A97 - 121
7X-RAY DIFFRACTION7chain 'A' and (resid 122 through 139 )A122 - 139
8X-RAY DIFFRACTION8chain 'A' and (resid 140 through 168 )A140 - 168

+
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