[English] 日本語
Yorodumi
- PDB-8gzc: Crystal structure of EP300 HAT domain in complex with compound 10 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8gzc
TitleCrystal structure of EP300 HAT domain in complex with compound 10
ComponentsHistone acetyltransferase p300
KeywordsTRANSFERASE / epigenetics / SBDD / Histone acetyltransferase
Function / homology
Function and homology information


behavioral defense response / negative regulation of protein oligomerization / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / swimming / peptide butyryltransferase activity / regulation of tubulin deacetylation ...behavioral defense response / negative regulation of protein oligomerization / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / swimming / peptide butyryltransferase activity / regulation of tubulin deacetylation / histone H2B acetyltransferase activity / internal protein amino acid acetylation / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / thigmotaxis / protein propionyltransferase activity / NOTCH2 intracellular domain regulates transcription / L-lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / positive regulation of TORC2 signaling / internal peptidyl-lysine acetylation / histone H4 acetyltransferase activity / cellular response to L-leucine / histone H3 acetyltransferase activity / NFE2L2 regulating ER-stress associated genes / protein N-acetyltransferase activity / acetylation-dependent protein binding / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / NGF-stimulated transcription / N-terminal peptidyl-lysine acetylation / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / STAT3 nuclear events downstream of ALK signaling / Polo-like kinase mediated events / NFE2L2 regulating MDR associated enzymes / TGFBR3 expression / positive regulation by host of viral transcription / regulation of androgen receptor signaling pathway / regulation of mitochondrion organization / 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 / face morphogenesis / Regulation of NFE2L2 gene expression / Regulation of gene expression by Hypoxia-inducible Factor / platelet formation / NOTCH3 Intracellular Domain Regulates Transcription / regulation of glycolytic process / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / megakaryocyte development / protein-lysine-acetyltransferase activity / STAT family protein binding / nuclear androgen receptor binding / acyltransferase activity / protein acetylation / Formation of paraxial mesoderm / positive regulation of transforming growth factor beta receptor signaling pathway / histone acetyltransferase activity / acetyltransferase activity / PI5P Regulates TP53 Acetylation / FOXO-mediated transcription of cell death genes / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / fat cell differentiation / stimulatory C-type lectin receptor signaling pathway / Zygotic genome activation (ZGA) / RUNX3 regulates p14-ARF / histone acetyltransferase complex / canonical NF-kappaB signal transduction / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / NF-kappaB binding / negative regulation of gluconeogenesis / cellular response to nutrient levels / somitogenesis / negative regulation of protein-containing complex assembly / pre-mRNA intronic binding / Attenuation phase / positive regulation of T-helper 17 cell lineage commitment / 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 / skeletal muscle tissue development / regulation of cellular response to heat
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, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
Chem-KQO / Histone acetyltransferase p300
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsTakahashi, M. / Hanzawa, H.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2023
Title: Discovery of DS-9300: A Highly Potent, Selective, and Once-Daily Oral EP300/CBP Histone Acetyltransferase Inhibitor.
Authors: Kanada, R. / Kagoshima, Y. / Suzuki, T. / Nakamura, A. / Funami, H. / Watanabe, J. / Asano, M. / Takahashi, M. / Ubukata, O. / Suzuki, K. / Aikawa, T. / Sato, K. / Goto, M. / Setsu, G. / ...Authors: Kanada, R. / Kagoshima, Y. / Suzuki, T. / Nakamura, A. / Funami, H. / Watanabe, J. / Asano, M. / Takahashi, M. / Ubukata, O. / Suzuki, K. / Aikawa, T. / Sato, K. / Goto, M. / Setsu, G. / Ito, K. / Kihara, K. / Kuroha, M. / Kohno, T. / Ogiwara, H. / Isoyama, T. / Tominaga, Y. / Higuchi, S. / Naito, H.
History
DepositionSep 26, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 11, 2023Provider: repository / Type: Initial release
Revision 1.1Jan 25, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 1.2Nov 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: Histone acetyltransferase p300
B: Histone acetyltransferase p300
hetero molecules


Theoretical massNumber of molelcules
Total (without water)106,13510
Polymers104,8112
Non-polymers1,3238
Water5,062281
1
A: Histone acetyltransferase p300
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,0675
Polymers52,4061
Non-polymers6624
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Histone acetyltransferase p300
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,0675
Polymers52,4061
Non-polymers6624
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)43.500, 89.350, 91.600
Angle α, β, γ (deg.)116.600, 95.180, 91.780
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Histone acetyltransferase p300 / p300 HAT / E1A-associated protein p300 / Histone butyryltransferase p300 / Histone ...p300 HAT / E1A-associated protein p300 / Histone butyryltransferase p300 / Histone crotonyltransferase p300 / Protein 2-hydroxyisobutyryltransferase p300 / Protein lactyltransferas p300 / Protein propionyltransferase p300


Mass: 52405.727 Da / Num. of mol.: 2 / Mutation: Y1467E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EP300, P300 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q09472, histone acetyltransferase
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-KQO / (2~{R},4~{R})-4-fluoranyl-1-[1-(4-methoxyphenyl)cyclohexyl]carbonyl-~{N}-(1~{H}-pyrazolo[4,3-b]pyridin-5-yl)pyrrolidine-2-carboxamide


Mass: 465.520 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C25H28FN5O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 281 / 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: 3.02 Å3/Da / Density % sol: 59.21 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: 15% PEG3350, 0.1 M HEPES

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Photon Factory / Beamline: BL-1A / Wavelength: 1.1 Å
DetectorType: DECTRIS EIGER X 4M / Detector: PIXEL / Date: Feb 22, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1 Å / Relative weight: 1
ReflectionResolution: 1.99→19.91 Å / Num. obs: 82690 / % possible obs: 96.8 % / Redundancy: 2.604 % / Biso Wilson estimate: 46.69 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.096 / Rrim(I) all: 0.118 / Χ2: 1.133 / Net I/σ(I): 5.74 / Num. measured all: 424926 / Scaling rejects: 673
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
1.99-2.041.5361.7450.291559612420101510.1672.46881.7
2.04-2.11.6271.3350.411865312200114640.2391.88894
2.1-2.161.6291.0470.521805211774110820.3141.48194.1
2.16-2.221.9081.1310.72097711514109930.371.47595.5
2.22-2.33.0491.0391.123376711144110760.2551.26199.4
2.3-2.383.0651.081.253259210682106350.511.3199.6
2.38-2.473.0290.6831.763120810382103020.6620.8399.2
2.47-2.573.0190.4852.433032510114100440.7950.58999.3
2.57-2.683.0060.3563.2428258946494000.8750.43399.3
2.68-2.812.9630.2714.1626835914090570.9140.33199.1
2.81-2.972.8770.1815.9425060876287100.9570.22399.4
2.97-3.152.6680.1347.5721815825881760.970.16799
3.15-3.362.8120.1039.9921615775276880.980.12799.2
3.36-3.632.8510.08512.3420390723471530.9860.10598.9
3.63-3.982.7020.06714.7417559660464980.990.08398.4
3.98-4.453.0190.05518.2117734595058750.9940.06698.7
4.45-5.143.0330.04619.4315849528052250.9950.05699
5.14-6.293.0260.04519.6813452451844450.9950.05498.4
6.29-8.92.9910.03720.7910102343833780.9970.04498.3
8.9-19.912.8120.03221.45087189818090.9970.03995.3

-
Processing

Software
NameVersionClassification
XSCALEdata scaling
PHENIX1.19.1_4122refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7VI0

7vi0


Resolution: 2→19.91 Å / SU ML: 0.35 / Cross valid method: THROUGHOUT / σ(F): 1.91 / Phase error: 28.95 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2268 4086 5 %
Rwork0.1945 77702 -
obs0.1961 81788 98.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 175.89 Å2 / Biso mean: 65.3943 Å2 / Biso min: 30.61 Å2
Refinement stepCycle: final / Resolution: 2→19.91 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6925 0 74 281 7280
Biso mean--52.13 57.25 -
Num. residues----880
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 29

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2-2.020.43021510.42712558270996
2.02-2.050.40081340.40092604273896
2.05-2.070.38031330.37362647278096
2.07-2.10.3541350.36082537267296
2.1-2.130.35381310.35912640277196
2.13-2.160.38111310.35492609274096
2.16-2.190.37951280.33262660278897
2.19-2.230.30241380.31112641277998
2.23-2.260.34471370.307327102847100
2.26-2.30.3791230.293827322855100
2.3-2.340.3111390.270627002839100
2.34-2.390.27281360.25327452881100
2.39-2.440.29131540.244626852839100
2.44-2.490.31671360.241826802816100
2.49-2.550.26281480.224527192867100
2.55-2.610.27541480.218426782826100
2.61-2.680.24771470.217227152862100
2.68-2.760.25391410.217327102851100
2.76-2.850.31211320.227127282860100
2.85-2.950.23631670.207526972864100
2.95-3.070.24131340.19327132847100
3.07-3.210.22931340.200826982832100
3.21-3.380.20531490.188227252874100
3.38-3.590.19421380.182327012839100
3.59-3.860.20281400.163927002840100
3.86-4.250.20051580.151126942852100
4.25-4.850.16711510.137427102861100
4.86-6.090.17751520.161426792831100
6.09-19.910.19261410.15272687282899
Refinement TLS params.Method: refined / Origin x: -21.6866 Å / Origin y: 7.5607 Å / Origin z: -2.5766 Å
111213212223313233
T0.3006 Å2-0.0338 Å2-0.0317 Å2-0.4092 Å2-0.0201 Å2--0.3218 Å2
L0.6377 °20.0031 °2-0.0697 °2-0.8124 °2-0.4679 °2--0.606 °2
S-0.0407 Å °0.046 Å °-0.0167 Å °-0.1119 Å °0.1155 Å °-0.0176 Å °0.0744 Å °-0.1869 Å °-0.0768 Å °
Refinement TLS groupSelection details: all

+
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