[English] 日本語
Yorodumi
- PDB-5hls: Crystal structure of the first bromodomain of human BRD4 bound to... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5hls
TitleCrystal structure of the first bromodomain of human BRD4 bound to CPI-0610
ComponentsBromodomain-containing protein 4
KeywordsTRANSCRIPTION / bromodomain
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II ...RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / chromosome / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / 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 / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
CPI-0610 / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.182 Å
AuthorsJayaram, H. / Poy, F. / Setser, J.W. / Bellon, S.F.
CitationJournal: J.Med.Chem. / Year: 2016
Title: Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials.
Authors: Albrecht, B.K. / Gehling, V.S. / Hewitt, M.C. / Vaswani, R.G. / Cote, A. / Leblanc, Y. / Nasveschuk, C.G. / Bellon, S. / Bergeron, L. / Campbell, R. / Cantone, N. / Cooper, M.R. / Cummings, ...Authors: Albrecht, B.K. / Gehling, V.S. / Hewitt, M.C. / Vaswani, R.G. / Cote, A. / Leblanc, Y. / Nasveschuk, C.G. / Bellon, S. / Bergeron, L. / Campbell, R. / Cantone, N. / Cooper, M.R. / Cummings, R.T. / Jayaram, H. / Joshi, S. / Mertz, J.A. / Neiss, A. / Normant, E. / O'Meara, M. / Pardo, E. / Poy, F. / Sandy, P. / Supko, J. / Sims, R.J. / Harmange, J.C. / Taylor, A.M. / Audia, J.E.
History
DepositionJan 15, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 10, 2016Provider: repository / Type: Initial release
Revision 1.1Mar 9, 2016Group: Database references
Revision 1.2Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
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)15,4922
Polymers15,1261
Non-polymers3661
Water2,756153
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area7460 Å2
MethodPISA
Unit cell
Length a, b, c (Å)33.788, 47.634, 77.775
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 15126.339 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-62G / CPI-0610 / 2-[(4S)-6-(4-chlorophenyl)-1-methyl-4H-[1,2]oxazolo[5,4-d][2]benzazepin-4-yl]acetamide


Mass: 365.813 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H16ClN3O2 / Comment: inhibitor*YM
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 153 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.07 Å3/Da / Density % sol: 40.55 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.8
Details: 3.4-3.8 M sodium formate, 0.1 M Tris pH 7.8, and 10% glycerol

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.54 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Nov 15, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.18→50 Å / Num. obs: 6289 / % possible obs: 90 % / Redundancy: 4.3 % / Rsym value: 0.108 / Net I/σ(I): 16.4
Reflection shellResolution: 2.18→2.26 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.25 / Mean I/σ(I) obs: 8.5 / % possible all: 70.2

-
Processing

Software
NameVersionClassification
REFMAC5.8.0069refinement
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2OSS

2oss


Resolution: 2.182→40.62 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.865 / SU B: 13.94 / SU ML: 0.204 / Cross valid method: THROUGHOUT / ESU R: 0.521 / ESU R Free: 0.296 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27717 435 6.9 %RANDOM
Rwork0.18601 ---
obs0.19204 5826 90.13 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 23.785 Å2
Baniso -1Baniso -2Baniso -3
1-3.78 Å20 Å2-0 Å2
2---2.66 Å20 Å2
3----1.12 Å2
Refinement stepCycle: 1 / Resolution: 2.182→40.62 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1061 0 26 153 1240
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.021125
X-RAY DIFFRACTIONr_bond_other_d00.021043
X-RAY DIFFRACTIONr_angle_refined_deg1.4161.9991537
X-RAY DIFFRACTIONr_angle_other_deg0.69332416
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3065128
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.19825.92654
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.77415196
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.354153
X-RAY DIFFRACTIONr_chiral_restr0.0840.2162
X-RAY DIFFRACTIONr_gen_planes_refined0.0140.0211299
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02244
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.0241.706509
X-RAY DIFFRACTIONr_mcbond_other2.021.702508
X-RAY DIFFRACTIONr_mcangle_it2.8112.55635
X-RAY DIFFRACTIONr_mcangle_other2.8112.554636
X-RAY DIFFRACTIONr_scbond_it2.3341.843616
X-RAY DIFFRACTIONr_scbond_other2.3071.859584
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other3.4552.711858
X-RAY DIFFRACTIONr_long_range_B_refined5.16415.5382617
X-RAY DIFFRACTIONr_long_range_B_other5.01115.312505
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.182→2.239 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.376 25 -
Rwork0.268 330 -
obs--70.02 %
Refinement TLS params.Method: refined / Origin x: 10.7307 Å / Origin y: 3.4475 Å / Origin z: 8.117 Å
111213212223313233
T0.0049 Å20.0029 Å2-0.0038 Å2-0.1197 Å20.0055 Å2--0.0044 Å2
L0.3515 °20.0979 °20.2522 °2-1.3889 °20.2552 °2--0.3496 °2
S0.0007 Å °-0.02 Å °-0.0045 Å °-0.0584 Å °-0.0126 Å °0.0705 Å °-0.0259 Å °-0.0358 Å °0.012 Å °

+
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