[English] 日本語
Yorodumi
- PDB-5w0i: CREBBP Bromodomain in complex with Cpd8 (1-(3-(7-(difluoromethyl)... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5w0i
TitleCREBBP Bromodomain in complex with Cpd8 (1-(3-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-1-(tetrahydrofuran-3-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)ethan-1-one)
ComponentsCREB-binding protein
KeywordsTRANSFERASE/INHIBITOR / CREBBP / Bromodomain / small molecule inhibitor / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


Activation of the TFAP2 (AP-2) family of transcription factors / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / Attenuation phase / Regulation of gene expression by Hypoxia-inducible Factor / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / cAMP response element binding protein binding / Formation of the beta-catenin:TCF transactivating complex ...Activation of the TFAP2 (AP-2) family of transcription factors / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / Attenuation phase / Regulation of gene expression by Hypoxia-inducible Factor / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / cAMP response element binding protein binding / Formation of the beta-catenin:TCF transactivating complex / NOTCH1 Intracellular Domain Regulates Transcription / RUNX3 regulates NOTCH signaling / Notch-HLH transcription pathway / positive regulation of cell adhesion molecule production / germ-line stem cell population maintenance / Regulation of lipid metabolism by PPARalpha / negative regulation of viral process / Cytoprotection by HMOX1 / CD209 (DC-SIGN) signaling / Estrogen-dependent gene expression / outer kinetochore / negative regulation of interferon-beta production / histone H3K27 acetyltransferase activity / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / MRF binding / peroxisome proliferator activated receptor binding / face morphogenesis / negative regulation of transcription by RNA polymerase I / positive regulation of dendritic spine development / peptide-lysine-N-acetyltransferase activity / cellular response to hepatocyte growth factor stimulus / positive regulation of transforming growth factor beta receptor signaling pathway / SMAD binding / behavioral response to cocaine / non-canonical NF-kappaB signal transduction / acetyltransferase activity / cellular response to nutrient levels / TFIIB-class transcription factor binding / histone acetyltransferase complex / positive regulation of G1/S transition of mitotic cell cycle / long-term memory / histone acetyltransferase activity / histone acetyltransferase / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / RNA polymerase II transcription regulatory region sequence-specific DNA binding / protein modification process / protein destabilization / transcription coactivator binding / PML body / chromatin DNA binding / cellular response to virus / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of protein localization to nucleus / RNA polymerase II transcription regulator complex / transcription corepressor activity / cellular response to UV / rhythmic process / positive regulation of DNA-binding transcription factor activity / disordered domain specific binding / p53 binding / DNA-binding transcription factor binding / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / damaged DNA binding / transcription coactivator activity / molecular adaptor activity / nuclear body / protein domain specific binding / chromatin binding / chromatin / protein-containing complex binding / positive regulation of gene expression / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytoplasm
Similarity search - Function
Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain ...Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain / CBP/p300-type histone acetyltransferase domain / CBP/p300, atypical RING domain superfamily / KIX domain / CREB-binding protein/p300, atypical RING domain / KIX domain profile. / CBP/p300-type histone acetyltransferase (HAT) domain profile. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Nuclear receptor coactivator, interlocking / Bromodomain-like / Histone Acetyltransferase; Chain A / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-9UA / Histone lysine acetyltransferase CREBBP
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.43 Å
AuthorsMurray, J.M.
CitationJournal: J. Med. Chem. / Year: 2017
Title: GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP).
Authors: Romero, F.A. / Murray, J. / Lai, K.W. / Tsui, V. / Albrecht, B.K. / An, L. / Beresini, M.H. / de Leon Boenig, G. / Bronner, S.M. / Chan, E.W. / Chen, K.X. / Chen, Z. / Choo, E.F. / Clagg, K. ...Authors: Romero, F.A. / Murray, J. / Lai, K.W. / Tsui, V. / Albrecht, B.K. / An, L. / Beresini, M.H. / de Leon Boenig, G. / Bronner, S.M. / Chan, E.W. / Chen, K.X. / Chen, Z. / Choo, E.F. / Clagg, K. / Clark, K. / Crawford, T.D. / Cyr, P. / de Almeida Nagata, D. / Gascoigne, K.E. / Grogan, J.L. / Hatzivassiliou, G. / Huang, W. / Hunsaker, T.L. / Kaufman, S. / Koenig, S.G. / Li, R. / Li, Y. / Liang, X. / Liao, J. / Liu, W. / Ly, J. / Maher, J. / Masui, C. / Merchant, M. / Ran, Y. / Taylor, A.M. / Wai, J. / Wang, F. / Wei, X. / Yu, D. / Zhu, B.Y. / Zhu, X. / Magnuson, S.
History
DepositionMay 30, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 7, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 4, 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: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,3755
Polymers17,6301
Non-polymers7454
Water2,648147
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)34.879, 48.602, 80.763
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein CREB-binding protein /


Mass: 17629.973 Da / Num. of mol.: 1 / Fragment: Bromodomain, UNP residues 1083-1198
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Crebbp, Cbp / Production host: Escherichia coli (E. coli) / References: UniProt: P45481, histone acetyltransferase
#2: Chemical ChemComp-9UA / 1-{3-[7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl]-1-[(3S)-oxolan-3-yl]-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl}ethan-1-one


Mass: 496.552 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H30F2N6O2
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE / Dimethyl sulfoxide


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


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


Mass: 18.015 Da / Num. of mol.: 147 / 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: 1.94 Å3/Da / Density % sol: 36.64 % / Mosaicity: 0.297 °
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 6.5 / Details: 0.2 M Li2SO4, 0.1M Bis-Tris pH 6.5, 23% PEG33500

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17B1 / Wavelength: 0.979 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 5, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.43→31.06 Å / Num. obs: 25858 / % possible obs: 98.8 % / Redundancy: 3.5 % / Biso Wilson estimate: 18.56 Å2 / Rmerge(I) obs: 0.094 / Rpim(I) all: 0.059 / Rrim(I) all: 0.112 / Χ2: 1.892 / Net I/σ(I): 10
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.43-1.483.40.530.7410.3280.6270.82698.5
1.48-1.543.50.3820.8380.2360.4520.8999.9
1.54-1.613.50.3030.9130.1850.3571.01399.9
1.61-1.73.60.2240.9480.1370.2641.07999.9
1.7-1.83.60.170.9690.1030.21.25899.9
1.8-1.943.60.1270.9780.0770.1491.56899.8
1.94-2.143.60.0990.9820.060.1161.918100
2.14-2.453.50.1020.9790.0620.123.21999.9
2.45-3.083.40.0970.970.0620.1164.16999.2
3.08-503.10.0720.9840.0470.0863.12491.7

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXdev_2747refinement
PDB_EXTRACT3.22data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdbid 5I8B

5i8b


Resolution: 1.43→31.06 Å / SU ML: 0.13 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 19.19
RfactorNum. reflection% reflection
Rfree0.192 1325 5.13 %
Rwork0.1742 --
obs0.1752 25805 98.83 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 53.51 Å2 / Biso mean: 23.7792 Å2 / Biso min: 13.35 Å2
Refinement stepCycle: final / Resolution: 1.43→31.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms957 0 86 147 1190
Biso mean--25.22 33.65 -
Num. residues----114
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0141127
X-RAY DIFFRACTIONf_angle_d1.4791545
X-RAY DIFFRACTIONf_chiral_restr0.103147
X-RAY DIFFRACTIONf_plane_restr0.011199
X-RAY DIFFRACTIONf_dihedral_angle_d23.354417
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.4298-1.48710.27211400.23932654279499
1.4871-1.55470.25121220.208727192841100
1.5547-1.63670.19241420.182127232865100
1.6367-1.73920.22791610.170427272888100
1.7392-1.87350.16871510.161527102861100
1.8735-2.0620.18391600.162227102870100
2.062-2.36030.18521540.156327522906100
2.3603-2.97340.21091540.18892769292399
2.9734-31.0670.17651410.17062716285793
Refinement TLS params.Method: refined / Origin x: 11.3868 Å / Origin y: 2.9864 Å / Origin z: 6.2134 Å
111213212223313233
T0.123 Å20.0067 Å20.0177 Å2-0.1376 Å20.0132 Å2--0.1505 Å2
L1.4478 °2-0.0484 °21.1573 °2-1.2488 °2-0.1906 °2--2.7161 °2
S0.0732 Å °-0.0569 Å °-0.0612 Å °0.0259 Å °0.0158 Å °0.0359 Å °0.1076 Å °-0.029 Å °0.0002 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA1084 - 1197
2X-RAY DIFFRACTION1allZ1
3X-RAY DIFFRACTION1allM1 - 147
4X-RAY DIFFRACTION1allS1 - 3

+
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