[English] 日本語
Yorodumi
- PDB-7xh6: Crystal structure of CBP bromodomain liganded with CCS1477 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7xh6
TitleCrystal structure of CBP bromodomain liganded with CCS1477
ComponentsCREB-binding protein
KeywordsPROTEIN BINDING / Histone acetyltransferase / CBP / Bromodomain
Function / homology
Function and homology information


peptide lactyltransferase (CoA-dependent) activity / Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters / NFE2L2 regulating ER-stress associated genes / NFE2L2 regulating inflammation associated genes / Activation of the TFAP2 (AP-2) family of transcription factors / The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / NFE2L2 regulates pentose phosphate pathway genes ...peptide lactyltransferase (CoA-dependent) activity / Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters / NFE2L2 regulating ER-stress associated genes / NFE2L2 regulating inflammation associated genes / Activation of the TFAP2 (AP-2) family of transcription factors / The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / NFE2L2 regulates pentose phosphate pathway genes / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / regulation of smoothened signaling pathway / NFE2L2 regulating MDR associated enzymes / MRF binding / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Regulation of FOXO transcriptional activity by acetylation / RUNX3 regulates NOTCH signaling / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes / negative regulation of transcription by RNA polymerase I / NOTCH3 Intracellular Domain Regulates Transcription / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / embryonic digit morphogenesis / protein acetylation / Notch-HLH transcription pathway / Formation of paraxial mesoderm / acetyltransferase activity / histone acetyltransferase activity / FOXO-mediated transcription of cell death genes / stimulatory C-type lectin receptor signaling pathway / positive regulation of transforming growth factor beta receptor signaling pathway / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / homeostatic process / histone acetyltransferase complex / Attenuation phase / cAMP/PKA signal transduction / protein-lysine-acetyltransferase activity / histone acetyltransferase / regulation of cellular response to heat / positive regulation of double-strand break repair via homologous recombination / Regulation of lipid metabolism by PPARalpha / NPAS4 regulates expression of target genes / canonical NF-kappaB signal transduction / Transcriptional and post-translational regulation of MITF-M expression and activity / BMAL1:CLOCK,NPAS2 activates circadian expression / CD209 (DC-SIGN) signaling / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / cellular response to nutrient levels / Heme signaling / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / Formation of the beta-catenin:TCF transactivating complex / chromatin DNA binding / Transcriptional regulation of white adipocyte differentiation / positive regulation of protein localization to nucleus / NOTCH1 Intracellular Domain Regulates Transcription / Evasion by RSV of host interferon responses / protein destabilization / Pre-NOTCH Transcription and Translation / tau protein binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / transcription coactivator binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / p53 binding / cellular response to UV / transcription corepressor activity / rhythmic process / HATs acetylate histones / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / protein-containing complex assembly / TRAF3-dependent IRF activation pathway / transcription regulator complex / DNA-binding transcription factor binding / Estrogen-dependent gene expression / damaged DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / response to hypoxia / transcription coactivator activity / nuclear body / chromatin binding / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / chromatin / SARS-CoV-2 activates/modulates innate and adaptive immune responses / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II
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 finger, ZZ type / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Nuclear receptor coactivator, interlocking / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Chem-JHL / CREB-binding protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsXu, H. / Xiang, Q. / Wang, C. / Zhang, C. / Luo, G. / Wu, X. / Zhang, Y. / Xu, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)22007088 China
CitationJournal: Biochem.Biophys.Res.Commun. / Year: 2022
Title: Structural insights revealed by the cocrystal structure of CCS1477 in complex with CBP bromodomain
Authors: Xu, H. / Luo, G. / Wu, T. / Hu, J. / Wang, C. / Wu, X. / Zhang, Y. / Xu, Y. / Xiang, Q.
History
DepositionApr 7, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 27, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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)33,0226
Polymers31,7832
Non-polymers1,2394
Water1,51384
1
A: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,5964
Polymers15,8911
Non-polymers7053
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area220 Å2
ΔGint1 kcal/mol
Surface area6830 Å2
MethodPISA
2
B: CREB-binding protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,4262
Polymers15,8911
Non-polymers5351
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area6670 Å2
MethodPISA
Unit cell
Length a, b, c (Å)48.457, 33.713, 78.342
Angle α, β, γ (deg.)90.000, 95.130, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein CREB-binding protein


Mass: 15891.296 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 1081-1197
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CREBBP, CBP / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q92793, histone acetyltransferase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#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-JHL / (6S)-1-[3,4-bis(fluoranyl)phenyl]-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(4-methoxycyclohexyl)benzimidazol-2-yl]piperidin-2-one / CCS1477 / Inobrodib


Mass: 534.597 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C30H32F2N4O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 84 / 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: 2.01 Å3/Da / Density % sol: 38.66 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.1M HEPES pH 7.5, 2% v/v Tacsimate pH 7.0, 20% w/v Polyethylene glycol 3350

-
Data collection

DiffractionMean temperature: 197 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.97915 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 18, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97915 Å / Relative weight: 1
ReflectionResolution: 1.75→78.03 Å / Num. obs: 25492 / % possible obs: 98.8 % / Redundancy: 6.5 % / CC1/2: 0.999 / Rmerge(I) obs: 0.054 / Rpim(I) all: 0.023 / Rrim(I) all: 0.059 / Net I/σ(I): 15.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.75-1.785.70.612798514020.810.2750.6732.595.8
8.92-19.625.60.02911272020.9990.0130.03138.290.3

-
Processing

Software
NameVersionClassification
Aimless0.5.32data scaling
REFMAC5.8.0189refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5XXH

5xxh


Resolution: 1.75→78.03 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.947 / SU B: 2.725 / SU ML: 0.087 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.123 / ESU R Free: 0.119 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2265 1225 4.8 %RANDOM
Rwork0.1895 ---
obs0.1913 24255 98.52 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 91.7 Å2 / Biso mean: 33.365 Å2 / Biso min: 16.41 Å2
Baniso -1Baniso -2Baniso -3
1-0.5 Å2-0 Å2-0.71 Å2
2---1.3 Å2-0 Å2
3---0.92 Å2
Refinement stepCycle: final / Resolution: 1.75→78.03 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1874 0 88 84 2046
Biso mean--31.67 33.56 -
Num. residues----225
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.022065
X-RAY DIFFRACTIONr_bond_other_d0.0040.021858
X-RAY DIFFRACTIONr_angle_refined_deg1.6722.0232819
X-RAY DIFFRACTIONr_angle_other_deg1.1683.0124333
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.065231
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.20624.706102
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.81415341
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.4921512
X-RAY DIFFRACTIONr_chiral_restr0.0930.2286
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0212240
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02414
LS refinement shellResolution: 1.75→1.795 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.334 84 -
Rwork0.247 1726 -
all-1810 -
obs--96.17 %

+
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