[English] 日本語
Yorodumi
- PDB-5d3s: First bromodomain of BRD4 bound to inhibitor XD44 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5d3s
TitleFirst bromodomain of BRD4 bound to inhibitor XD44
ComponentsBromodomain-containing protein 4
KeywordsTRANSCRIPTION / Gene regulation / Bromodomain / 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-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-579 / (R,R)-2,3-BUTANEDIOL / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsWohlwend, D. / Huegle, M.
Funding support Germany, 1items
OrganizationGrant numberCountry
German Research FoundationWO2012/1-1 Germany
CitationJournal: J.Med.Chem. / Year: 2016
Title: 4-Acyl Pyrrole Derivatives Yield Novel Vectors for Designing Inhibitors of the Acetyl-Lysine Recognition Site of BRD4(1).
Authors: Hugle, M. / Lucas, X. / Weitzel, G. / Ostrovskyi, D. / Breit, B. / Gerhardt, S. / Einsle, O. / Gunther, S. / Wohlwend, D.
History
DepositionAug 6, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Jan 20, 2016Provider: repository / Type: Initial release
Revision 1.1Mar 9, 2016Group: Database references
Revision 1.2Sep 6, 2017Group: Advisory / Author supporting evidence / Category: pdbx_audit_support / pdbx_unobs_or_zero_occ_atoms / Item: _pdbx_audit_support.funding_organization
Revision 1.3May 8, 2024Group: Advisory / Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms
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)15,6184
Polymers15,0121
Non-polymers6063
Water2,144119
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area450 Å2
ΔGint4 kcal/mol
Surface area7600 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.480, 49.510, 57.790
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: 15012.301 Da / Num. of mol.: 1 / Fragment: First bromodomain, UNP residues 44-168 / Mutation: T43M
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-579 / 4-acetyl-3-ethyl-N-[4-fluoro-3-(morpholin-4-ylsulfonyl)phenyl]-5-methyl-1H-pyrrole-2-carboxamide


Mass: 437.485 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H24FN3O5S
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-BU3 / (R,R)-2,3-BUTANEDIOL


Mass: 90.121 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 119 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 1.88 Å3/Da / Density % sol: 34.61 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / Details: PEG3350, Bis-Tris

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Dec 17, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.75→25 Å / Num. obs: 11878 / % possible obs: 99.6 % / Redundancy: 3.8 % / Rmerge(I) obs: 0.093 / Net I/σ(I): 12.6
Reflection shellResolution: 1.75→1.84 Å / Rmerge(I) obs: 0.418 / Mean I/σ(I) obs: 4.7 / Num. unique all: 1690 / % possible all: 99.8

-
Processing

Software
NameVersionClassification
REFMAC5.8.0073refinement
SCALA3.3.21data scaling
PHASER2.5.6phasing
iMOSFLMdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.75→25 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.95 / SU B: 5.054 / SU ML: 0.082 / Cross valid method: THROUGHOUT / ESU R: 0.147 / ESU R Free: 0.12 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.19513 1151 9.7 %RANDOM
Rwork0.17575 ---
obs0.17763 10693 99.37 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 16.441 Å2
Baniso -1Baniso -2Baniso -3
1--0.04 Å20 Å2-0 Å2
2--0.55 Å20 Å2
3----0.51 Å2
Refinement stepCycle: 1 / Resolution: 1.75→25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1046 0 40 119 1205
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.021146
X-RAY DIFFRACTIONr_bond_other_d0.0010.021093
X-RAY DIFFRACTIONr_angle_refined_deg1.3562.0081566
X-RAY DIFFRACTIONr_angle_other_deg0.77332523
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.7485131
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.48725.92654
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.68415199
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.207153
X-RAY DIFFRACTIONr_chiral_restr0.0720.2164
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0211289
X-RAY DIFFRACTIONr_gen_planes_other0.0040.02256
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_it0.3860.765518
X-RAY DIFFRACTIONr_mcbond_other0.3870.763517
X-RAY DIFFRACTIONr_mcangle_it0.6771.142651
X-RAY DIFFRACTIONr_mcangle_other0.6771.145652
X-RAY DIFFRACTIONr_scbond_it0.6850.918628
X-RAY DIFFRACTIONr_scbond_other0.6840.921629
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other1.0021.346916
X-RAY DIFFRACTIONr_long_range_B_refined3.3337.9174843
X-RAY DIFFRACTIONr_long_range_B_other3.0637.5554740
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.75→1.795 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.298 86 -
Rwork0.236 782 -
obs--99.77 %
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)
17.0033-0.55014.71796.1722-1.14386.02040.0930.93180.0194-0.1266-0.15710.01590.01160.88320.06410.03590.00070.04180.150400.068318.2544-9.9158-23.5208
27.8136-1.85911.58980.8487-0.45880.3408-0.01380.121-0.1878-0.04820.0067-0.15530.01510.0320.00710.2049-0.01490.02750.2295-0.0130.19687.5908-6.248-37.1042
32.027-0.05981.01991.57810.14052.187-0.1356-0.0460.1520.06450.0128-0.057-0.16920.08390.12280.028-0.0091-0.00790.0113-0.00510.02098.4625-6.0006-16.6368
41.7148-0.48162.0491.4747-1.40383.62160.022-0.0828-0.0750.06940.03940.06770.0554-0.0955-0.06140.017-0.00660.01530.0214-0.00960.02315.1249-13.0268-13.5648
54.7455-0.39772.55712.95010.49237.3982-0.097-0.01390.0253-0.17370.07960.1855-0.0217-0.31090.01740.0417-0.01180.03140.066-0.00510.1041-6.2379-6.6416-14.8567
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A43 - 52
2X-RAY DIFFRACTION2A53 - 57
3X-RAY DIFFRACTION3A58 - 117
4X-RAY DIFFRACTION4A118 - 152
5X-RAY DIFFRACTION5A153 - 167

+
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