[English] 日本語
Yorodumi
- PDB-6ps9: Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ps9
TitleCrystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 17 (5-{2-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]ethyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one)
ComponentsBromodomain-containing protein 4
KeywordsPROTEIN BINDING / BRD4 BD1 / Bromodomain / Olinone
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-like ...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-like / Histone Acetyltransferase; Chain A / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-Y17 / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.21 Å
AuthorsIlyichova, O.V. / Scanlon, M.J.
CitationJournal: Bioorg.Med.Chem. / Year: 2019
Title: Synthesis and elaboration of N-methylpyrrolidone as an acetamide fragment substitute in bromodomain inhibition.
Authors: Hilton-Proctor, J.P. / Ilyichova, O. / Zheng, Z. / Jennings, I.G. / Johnstone, R.W. / Shortt, J. / Mountford, S.J. / Scanlon, M.J. / Thompson, P.E.
History
DepositionJul 12, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 27, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 4, 2019Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)15,2802
Polymers14,9681
Non-polymers3111
Water4,107228
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area7470 Å2
MethodPISA
Unit cell
Length a, b, c (Å)37.944, 44.141, 78.697
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
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

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


Mass: 14968.182 Da / Num. of mol.: 1 / Fragment: UNP residues 44-168
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pET28(a) / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: O60885
#2: Chemical ChemComp-Y17 / 5-{2-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]ethyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one


Mass: 311.378 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H21N3O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 228 / 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: 2.2 Å3/Da / Density % sol: 44.13 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop
Details: 0.2 M sodium nitrate, 35% PEG3350, 6% v/v ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.94645 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 11, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.94645 Å / Relative weight: 1
ReflectionResolution: 1.21→44.14 Å / Num. obs: 40846 / % possible obs: 99.7 % / Redundancy: 7.3 % / Biso Wilson estimate: 12.06 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.049 / Rpim(I) all: 0.029 / Rrim(I) all: 0.057 / Net I/σ(I): 17.6
Reflection shellResolution: 1.21→1.23 Å / Redundancy: 6.8 % / Rmerge(I) obs: 0.653 / Mean I/σ(I) obs: 2.8 / Num. unique obs: 1895 / CC1/2: 0.834 / Rpim(I) all: 0.391 / Rrim(I) all: 0.763 / % possible all: 94

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 5DW2

5dw2


Resolution: 1.21→38.5 Å / SU ML: 0.1008 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 15.9002
RfactorNum. reflection% reflection
Rfree0.1635 1995 4.9 %
Rwork0.143 --
obs0.144 40711 99.49 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 17.23 Å2
Refinement stepCycle: LAST / Resolution: 1.21→38.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1043 0 23 228 1294
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00841188
X-RAY DIFFRACTIONf_angle_d0.96191637
X-RAY DIFFRACTIONf_chiral_restr0.0668173
X-RAY DIFFRACTIONf_plane_restr0.007214
X-RAY DIFFRACTIONf_dihedral_angle_d6.4183714
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.21-1.240.23931510.22882607X-RAY DIFFRACTION95.7
1.24-1.280.21871400.17452711X-RAY DIFFRACTION100
1.28-1.310.2411330.20172761X-RAY DIFFRACTION99.9
1.31-1.360.19111380.14752768X-RAY DIFFRACTION100
1.36-1.40.18281490.13672710X-RAY DIFFRACTION99.97
1.4-1.460.18161450.12592770X-RAY DIFFRACTION100
1.46-1.530.15691290.11452761X-RAY DIFFRACTION100
1.53-1.610.1671480.11412743X-RAY DIFFRACTION100
1.61-1.710.14511530.11772762X-RAY DIFFRACTION100
1.71-1.840.17981280.13012796X-RAY DIFFRACTION99.97
1.84-2.030.16451500.14932733X-RAY DIFFRACTION98.9
2.03-2.320.16981490.13822778X-RAY DIFFRACTION98.85
2.32-2.920.15681390.14562851X-RAY DIFFRACTION100
2.92-38.50.14181430.14692965X-RAY DIFFRACTION99.62

+
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