[English] 日本語
Yorodumi
- PDB-6ay3: CREBBP bromodomain in complex with Cpd16 (5-(7-(difluoromethyl)-6... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ay3
TitleCREBBP bromodomain in complex with Cpd16 (5-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-N-methyl-1H-indole-3-carboxamide)
ComponentsCREB-binding protein
KeywordsTRANSFERASE/TRANSFERASE inhibitor / CREBBP / Bromodomain / TRANSFERASE-TRANSFERASE inhibitor complex
Function / homology
Function and homology information


peptide lactyltransferase (CoA-dependent) activity / NFE2L2 regulating ER-stress associated genes / protein N-acetyltransferase activity / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / N-terminal peptidyl-lysine acetylation / regulation of smoothened signaling pathway / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / NFE2L2 regulating MDR associated enzymes ...peptide lactyltransferase (CoA-dependent) activity / NFE2L2 regulating ER-stress associated genes / protein N-acetyltransferase activity / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / N-terminal peptidyl-lysine acetylation / regulation of smoothened signaling pathway / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / NFE2L2 regulating MDR associated enzymes / MRF binding / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of FOXO transcriptional activity by acetylation / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / RUNX3 regulates NOTCH signaling / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / Regulation of gene expression by Hypoxia-inducible Factor / NOTCH3 Intracellular Domain Regulates Transcription / negative regulation of transcription by RNA polymerase I / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / protein-lysine-acetyltransferase activity / embryonic digit morphogenesis / protein acetylation / homeostatic process / Notch-HLH transcription pathway / Formation of paraxial mesoderm / positive regulation of transforming growth factor beta receptor signaling pathway / histone acetyltransferase activity / acetyltransferase activity / FOXO-mediated transcription of cell death genes / stimulatory C-type lectin receptor signaling pathway / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / histone acetyltransferase complex / canonical NF-kappaB signal transduction / cellular response to nutrient levels / Attenuation phase / positive regulation of double-strand break repair via homologous recombination / histone H4K16 acetyltransferase activity / histone H3K56 acetyltransferase activity / histone H3K23 acetyltransferase activity / histone H2AK5 acetyltransferase activity / histone H2AK9 acetyltransferase activity / histone H2BK5 acetyltransferase activity / histone H2BK12 acetyltransferase activity / histone H3K4 acetyltransferase activity / histone H3K27 acetyltransferase activity / histone H3K36 acetyltransferase activity / histone H3K122 acetyltransferase activity / histone H3K18 acetyltransferase activity / histone H3K9 acetyltransferase activity / histone H3K14 acetyltransferase activity / histone H4K5 acetyltransferase activity / histone H4K8 acetyltransferase activity / histone H4K12 acetyltransferase activity / regulation of cellular response to heat / histone acetyltransferase / : / Regulation of lipid metabolism by PPARalpha / NPAS4 regulates expression of target genes / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / Transcriptional and post-translational regulation of MITF-M expression and activity / CD209 (DC-SIGN) signaling / BMAL1:CLOCK,NPAS2 activates circadian expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / Formation of the beta-catenin:TCF transactivating complex / Heme signaling / Transcriptional activation of mitochondrial biogenesis / transcription coactivator binding / PPARA activates gene expression / protein destabilization / Cytoprotection by HMOX1 / Evasion by RSV of host interferon responses / chromatin DNA binding / Transcriptional regulation of white adipocyte differentiation / Pre-NOTCH Transcription and Translation / positive regulation of protein localization to nucleus / NOTCH1 Intracellular Domain Regulates Transcription / tau protein binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Activation of anterior HOX genes in hindbrain development during early embryogenesis / transcription corepressor activity / cellular response to UV / p53 binding / rhythmic process / : / HATs acetylate histones / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / TRAF3-dependent IRF activation pathway / protein-containing complex assembly / DNA-binding transcription factor binding / transcription regulator complex / Estrogen-dependent gene expression / RNA polymerase II-specific DNA-binding transcription factor binding
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 / : / Histone acetyltransferase p300-like, PHD 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 / : / Histone acetyltransferase p300-like, PHD domain / 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-C3J / CREB-binding protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.391 Å
AuthorsMurray, J.M.
CitationJournal: J. Med. Chem. / Year: 2017
Title: A Unique Approach to Design Potent and Selective Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP) Inhibitors.
Authors: Bronner, S.M. / Murray, J. / Romero, F.A. / Lai, K.W. / Tsui, V. / Cyr, P. / Beresini, M.H. / de Leon Boenig, G. / Chen, Z. / Choo, E.F. / Clark, K.R. / Crawford, T.D. / Jayaram, H. / ...Authors: Bronner, S.M. / Murray, J. / Romero, F.A. / Lai, K.W. / Tsui, V. / Cyr, P. / Beresini, M.H. / de Leon Boenig, G. / Chen, Z. / Choo, E.F. / Clark, K.R. / Crawford, T.D. / Jayaram, H. / Kaufman, S. / Li, R. / Li, Y. / Liao, J. / Liang, X. / Liu, W. / Ly, J. / Maher, J. / Wai, J. / Wang, F. / Zheng, A. / Zhu, X. / Magnuson, S.
History
DepositionSep 7, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 21, 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
B: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,4557
Polymers27,4372
Non-polymers1,0185
Water5,927329
1
A: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,2394
Polymers13,7191
Non-polymers5213
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)14,2163
Polymers13,7191
Non-polymers4982
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)33.910, 80.448, 48.522
Angle α, β, γ (deg.)90.000, 109.060, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein CREB-binding protein


Mass: 13718.702 Da / Num. of mol.: 2 / Fragment: Bromodomain (UNP residue 1083-1197)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CREBBP, CBP / Production host: Escherichia coli (E. coli) / References: UniProt: Q92793, histone acetyltransferase
#2: Chemical ChemComp-C3J / 5-[7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl]-N-methyl-1H-indole-3-carboxamide


Mass: 435.469 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H23F2N5O
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 329 / 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: 2.28 Å3/Da / Density % sol: 46.05 % / Mosaicity: 0.578 °
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 6.5 / Details: 0.2M MgCl2, 0.1M Bis-Tris pH6.5, 22% PEG3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.9793 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Mar 23, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9793 Å / Relative weight: 1
ReflectionResolution: 1.39→50 Å / Num. obs: 49193 / % possible obs: 99.8 % / Redundancy: 3.7 % / Biso Wilson estimate: 12.16 Å2 / Rmerge(I) obs: 0.084 / Rpim(I) all: 0.051 / Rrim(I) all: 0.099 / Χ2: 1.116 / Net I/σ(I): 8 / Num. measured all: 181476
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.39-1.443.60.67748890.6530.4170.7981.17899.9
1.44-1.53.60.48649200.7990.2990.5721.205100
1.5-1.573.70.3548900.880.2140.4111.16699.9
1.57-1.653.70.2749250.9240.1660.3181.16699.9
1.65-1.753.70.19848910.9580.1210.2331.13899.8
1.75-1.893.70.14549460.9730.0880.171.09599.9
1.89-2.083.70.1148990.9840.0660.1281.05899.8
2.08-2.383.70.09149100.9850.0550.1071.08199.8
2.38-2.993.70.06649260.9920.040.0771.06799.6
2.99-503.80.0549970.9950.030.0581.01599.4

-
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: 1.391→29.775 Å / SU ML: 0.2 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 25.91
RfactorNum. reflection% reflection
Rfree0.2372 2507 5.1 %
Rwork0.2017 --
obs0.2036 49156 99.65 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 65.35 Å2 / Biso mean: 18.1426 Å2 / Biso min: 6.75 Å2
Refinement stepCycle: final / Resolution: 1.391→29.775 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1932 0 73 329 2334
Biso mean--14.56 27.74 -
Num. residues----230
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0142200
X-RAY DIFFRACTIONf_angle_d1.4213004
X-RAY DIFFRACTIONf_chiral_restr0.103296
X-RAY DIFFRACTIONf_plane_restr0.01395
X-RAY DIFFRACTIONf_dihedral_angle_d21.189839
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 18

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.3908-1.41750.3911380.32012533267197
1.4175-1.44640.28291320.292925732705100
1.4464-1.47790.28641410.26725992740100
1.4779-1.51230.28751460.241725612707100
1.5123-1.55010.27221440.240325812725100
1.5501-1.5920.29671130.220126282741100
1.592-1.63880.26381380.210125952733100
1.6388-1.69170.29031410.212325872728100
1.6917-1.75220.23411440.205225872731100
1.7522-1.82230.25041560.197825732729100
1.8223-1.90530.241540.199425862740100
1.9053-2.00570.23091330.204226042737100
2.0057-2.13130.23971420.198625992741100
2.1313-2.29580.24841480.196925862734100
2.2958-2.52670.22211160.20062591270799
2.5267-2.89210.23131370.202326252762100
2.8921-3.64270.21511380.178926162754100
3.6427-29.7820.1971460.17632625277199
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)
10.65250.0950.02991.1252-0.32450.5761-0.0006-0.0167-0.02230.01780.01880.08270.0092-0.02550.00260.070.00170.00920.08570.01610.095.035-6.83719.677
20.8713-0.33790.13071.1086-0.18450.86420.0440.08860.0205-0.1402-0.0439-0.01-0.0308-0.00090.00490.10010.005-0.00170.09510.00230.07721.9876.5130.896
32.04630.82890.07970.7438-0.05590.0222-0.0008-0.0810.00340.11560.002-0.0201-0.01410.022-0.07410.1482-0.00610.01830.1456-0.01210.086833.396-2.0221.318
41.2734-0.91040.10751.3199-0.23910.04840.03040.11420.0069-0.121-0.0975-0.06750.04490.0852-0.16830.12180.0093-0.0010.130.01090.064416.5851.67119.748
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND RESID 1083:1197 )A1083 - 1197
2X-RAY DIFFRACTION2( CHAIN B AND RESID 1083:1197 )B1083 - 1197
3X-RAY DIFFRACTION3( CHAIN B AND RESID 1201:1201 )B1201
4X-RAY DIFFRACTION4( CHAIN A AND RESID 1201:1201 )A1201

+
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