[English] 日本語
Yorodumi
- PDB-8dkb: Crystal Structure of human YEATS4 in complex with Pfizer small mo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8dkb
TitleCrystal Structure of human YEATS4 in complex with Pfizer small molecule compound 3b
ComponentsYEATS domain-containing protein 4
KeywordsPROTEIN BINDING / histone binding / lysine-acetylated histone binding
Function / homology
Function and homology information


modification-dependent protein binding / regulation of double-strand break repair / Activation of the TFAP2 (AP-2) family of transcription factors / NuA4 histone acetyltransferase complex / positive regulation of double-strand break repair via homologous recombination / lysine-acetylated histone binding / structural constituent of cytoskeleton / nuclear matrix / nucleosome / mitotic cell cycle ...modification-dependent protein binding / regulation of double-strand break repair / Activation of the TFAP2 (AP-2) family of transcription factors / NuA4 histone acetyltransferase complex / positive regulation of double-strand break repair via homologous recombination / lysine-acetylated histone binding / structural constituent of cytoskeleton / nuclear matrix / nucleosome / mitotic cell cycle / HATs acetylate histones / histone binding / regulation of apoptotic process / nuclear membrane / regulation of cell cycle / chromatin remodeling / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / nucleoplasm / nucleus
Similarity search - Function
YEATS / YEATS superfamily / YEATS family / YEATS domain profile.
Similarity search - Domain/homology
Chem-SJI / YEATS domain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.58 Å
AuthorsDias, J.M. / Byrnes, L.J. / Varghese, A.H.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J.Med.Chem. / Year: 2023
Title: Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4.
Authors: Londregan, A.T. / Aitmakhanova, K. / Bennett, J. / Byrnes, L.J. / Canterbury, D.P. / Cheng, X. / Christott, T. / Clemens, J. / Coffey, S.B. / Dias, J.M. / Dowling, M.S. / Farnie, G. / ...Authors: Londregan, A.T. / Aitmakhanova, K. / Bennett, J. / Byrnes, L.J. / Canterbury, D.P. / Cheng, X. / Christott, T. / Clemens, J. / Coffey, S.B. / Dias, J.M. / Dowling, M.S. / Farnie, G. / Fedorov, O. / Fennell, K.F. / Gamble, V. / Gileadi, C. / Giroud, C. / Harris, M.R. / Hollingshead, B.D. / Huber, K. / Korczynska, M. / Lapham, K. / Loria, P.M. / Narayanan, A. / Owen, D.R. / Raux, B. / Sahasrabudhe, P.V. / Ruggeri, R.B. / Saez, L.D. / Stock, I.A. / Thuma, B.A. / Tsai, A. / Varghese, A.E.
History
DepositionJul 5, 2022Deposition site: RCSB / Processing site: RCSB
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 1.2Oct 25, 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: YEATS domain-containing protein 4
B: YEATS domain-containing protein 4
C: YEATS domain-containing protein 4
D: YEATS domain-containing protein 4
E: YEATS domain-containing protein 4
F: YEATS domain-containing protein 4
G: YEATS domain-containing protein 4
H: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)149,14816
Polymers145,8478
Non-polymers3,3018
Water6,017334
1
A: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
5
E: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
6
F: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
7
G: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
8
H: YEATS domain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,6432
Polymers18,2311
Non-polymers4131
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)60.600, 109.300, 103.830
Angle α, β, γ (deg.)90.000, 95.680, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
YEATS domain-containing protein 4 / Glioma-amplified sequence 41 / Gas41 / NuMA-binding protein 1 / NuBI-1 / NuBI1


Mass: 18230.885 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: YEATS4, GAS41 / Production host: Escherichia coli (E. coli) / References: UniProt: O95619
#2: Chemical
ChemComp-SJI / N-ethyl-1-{(3S,4S)-1-[(1-hydroxycyclohexyl)methyl]-3-methylpiperidin-4-yl}-2-methyl-1H-benzimidazole-5-carboxamide


Mass: 412.568 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C24H36N4O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 334 / 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: 2.35 Å3/Da / Density % sol: 47.57 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.1 M sodium citrate tribasic dihydrate (pH 5.6), 2% (v/v) tacsimate (pH 5.0), and 16% PEG 3350, 0.1M Ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 10, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.58→103.32 Å / Num. obs: 26291 / % possible obs: 62 % / Redundancy: 3.4 % / CC1/2: 0.994 / Rsym value: 0.117 / Net I/σ(I): 8.7
Reflection shellResolution: 2.582→2.803 Å / Redundancy: 3.4 % / Mean I/σ(I) obs: 1.3 / Num. unique obs: 1316 / CC1/2: 0.51 / Rsym value: 1.04 / % possible all: 14.2

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
PDB_EXTRACT3.27data extraction
autoPROCdata reduction
autoPROCdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5VNA

5vna


Resolution: 2.58→41.3 Å / Cor.coef. Fo:Fc: 0.926 / Cor.coef. Fo:Fc free: 0.89 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.389
RfactorNum. reflection% reflectionSelection details
Rfree0.226 1286 4.89 %RANDOM
Rwork0.171 ---
obs0.174 26282 62 %-
Displacement parametersBiso max: 197.24 Å2 / Biso mean: 72.9 Å2 / Biso min: 15.6 Å2
Baniso -1Baniso -2Baniso -3
1-14.7564 Å20 Å2-9.3777 Å2
2---7.2453 Å20 Å2
3----7.5111 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: final / Resolution: 2.58→41.3 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8422 0 240 334 8996
Biso mean--73.6 44.2 -
Num. residues----1011
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d3109SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes1562HARMONIC5
X-RAY DIFFRACTIONt_it8935HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1123SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact9818SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d8935HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg12138HARMONIC21.09
X-RAY DIFFRACTIONt_omega_torsion3.25
X-RAY DIFFRACTIONt_other_torsion17.84
LS refinement shellResolution: 2.58→2.73 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.339 20 3.8 %
Rwork0.2169 506 -
all0.221 526 -
obs--8.31 %
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)
10.69131.8601-1.76392.4468-2.97751.41660.16440.43010.30560.20440.32520.1438-0.6382-0.1652-0.48960.3825-0.0075-0.14150.0270.0839-0.0947-3.9834-3.069435.8681
21.20531.6727-1.11662.402-1.54650.085-0.28010.31230.0542-0.25790.17220.06720.5245-0.53890.10790.14140.0607-0.22580.02730.1278-0.11415.315621.18464.1752
33.6674-0.76960.09445.82770.7865.0710.230.1961-0.0565-0.3692-0.1983-0.38680.0781-0.0445-0.03160.0474-0.0277-0.0846-0.46350.0242-0.39187.254324.218164.1821
42.75090.53211.503810.9062.01618.2053-0.07640.0996-0.02930.9920.1331-0.82050.14820.1373-0.0567-0.1079-0.0164-0.3139-0.66020.0544-0.51869.3916-2.073358.9609
54.247-0.20790.19526.2362-2.04415.77070.1418-0.2961-0.4029-0.59350.03350.85020.634-0.712-0.1753-0.0336-0.1142-0.2179-0.4335-0.0401-0.3506-18.419127.074458.9062
66.6827-2.4564-0.33029.2691-0.07335.2005-0.18770.17150.43280.87560.2165-1.54970.06740.1747-0.0289-0.2426-0.0314-0.4624-0.6674-0.07-0.2444-20.719418.209913.5432
73.8656-0.50160.96937.65011.32687.2302-0.2111-0.09940.21110.0540.2405-0.4032-0.19570.2355-0.0295-0.02880.0932-0.2466-0.3692-0.0824-0.2361-17.1882-7.85539.4331
83.0825-0.69621.301212.67920.09284.1634-0.1183-0.32740.69121.61740.0825-0.7344-0.4858-0.32520.03580.13420.0223-0.3846-0.64220.038-0.53926.039645.453115.5826
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A19 - 144
2X-RAY DIFFRACTION2{ B|* }B20 - 145
3X-RAY DIFFRACTION3{ C|* }C20 - 148
4X-RAY DIFFRACTION4{ D|* }D20 - 144
5X-RAY DIFFRACTION5{ E|* }E19 - 145
6X-RAY DIFFRACTION6{ F|* }F19 - 144
7X-RAY DIFFRACTION7{ G|* }G19 - 144
8X-RAY DIFFRACTION8{ H|* }H21 - 146

+
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://pdbjlvh1.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