[English] 日本語
Yorodumi
- PDB-7lrk: Crystal structure of BPTF bromodomain in complex with inhibitor P... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lrk
TitleCrystal structure of BPTF bromodomain in complex with inhibitor Pdy-3-093
ComponentsNucleosome-remodeling factor subunit BPTF
KeywordsGENE REGULATION/INHIBITOR / BPTF / bromodomain / inhibitor / GENE REGULATION / GENE REGULATION-INHIBITOR complex
Function / homology
Function and homology information


NURF complex / endoderm development / anterior/posterior pattern specification / ATPase complex / : / embryonic placenta development / cellular response to nerve growth factor stimulus / brain development / cell body / sequence-specific DNA binding ...NURF complex / endoderm development / anterior/posterior pattern specification / ATPase complex / : / embryonic placenta development / cellular response to nerve growth factor stimulus / brain development / cell body / sequence-specific DNA binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin remodeling / dendrite / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / chromatin / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / extracellular exosome / zinc ion binding / nucleoplasm / nucleus / cytoplasm
Similarity search - Function
Nucleosome-remodeling factor subunit BPTF / DDT domain / DDT domain / WHIM2 domain / Williams-Beuren syndrome DDT (WSD), D-TOX E motif / DDT domain profile. / domain in different transcription and chromosome remodeling factors / Zinc finger, PHD-type, conserved site / PHD-finger / Zinc finger PHD-type signature. ...Nucleosome-remodeling factor subunit BPTF / DDT domain / DDT domain / WHIM2 domain / Williams-Beuren syndrome DDT (WSD), D-TOX E motif / DDT domain profile. / domain in different transcription and chromosome remodeling factors / Zinc finger, PHD-type, conserved site / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Bromodomain-like / Histone Acetyltransferase; Chain A / Zinc finger, FYVE/PHD-type / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-YC4 / Nucleosome-remodeling factor subunit BPTF
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.44 Å
AuthorsChan, A. / Schonbrunn, E.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM121414-01 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)P30-CA076292 United States
CitationJournal: J.Med.Chem. / Year: 2021
Title: New Design Rules for Developing Potent Cell-Active Inhibitors of the Nucleosome Remodeling Factor (NURF) via BPTF Bromodomain Inhibition.
Authors: Zahid, H. / Buchholz, C.R. / Singh, M. / Ciccone, M.F. / Chan, A. / Nithianantham, S. / Shi, K. / Aihara, H. / Fischer, M. / Schonbrunn, E. / Dos Santos, C.O. / Landry, J.W. / Pomerantz, W.C.K.
History
DepositionFeb 16, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 10, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Feb 21, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Nucleosome-remodeling factor subunit BPTF
B: Nucleosome-remodeling factor subunit BPTF
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,11316
Polymers28,9112
Non-polymers1,20214
Water5,080282
1
A: Nucleosome-remodeling factor subunit BPTF
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,0578
Polymers14,4551
Non-polymers6017
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Nucleosome-remodeling factor subunit BPTF
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,0578
Polymers14,4551
Non-polymers6017
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)58.310, 27.070, 76.720
Angle α, β, γ (deg.)90.000, 93.670, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Nucleosome-remodeling factor subunit BPTF / Bromodomain and PHD finger-containing transcription factor / Fetal Alz-50 clone 1 protein / Fetal ...Bromodomain and PHD finger-containing transcription factor / Fetal Alz-50 clone 1 protein / Fetal Alzheimer antigen


Mass: 14455.415 Da / Num. of mol.: 2 / Fragment: BPTF bromodomain (uniprot residues 2917-3037)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BPTF, FAC1, FALZ / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q12830
#2: Chemical ChemComp-YC4 / 4-chloranyl-2-methyl-5-[[(3~{S})-pyrrolidin-3-yl]amino]pyridazin-3-one


Mass: 228.679 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C9H13ClN4O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 282 / 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: 2.09 Å3/Da / Density % sol: 41.15 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 0.2M Lithium sulfate monohydrate, 0.1M Bis-Tris pH 6.5 and 25% polyethylene glycol 3,350

-
Data collection

DiffractionMean temperature: 93 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
DetectorType: RAYONIX MX300-HS / Detector: CCD / Date: Nov 16, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.44→38.3 Å / Num. obs: 43465 / % possible obs: 98.3 % / Redundancy: 3.5 % / CC1/2: 0.998 / Rmerge(I) obs: 0.06 / Rrim(I) all: 0.071 / Net I/σ(I): 16.7
Reflection shellResolution: 1.44→1.48 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.371 / Mean I/σ(I) obs: 3.6 / Num. unique obs: 2851 / CC1/2: 0.876 / Rrim(I) all: 0.453 / % possible all: 88.1

-
Processing

Software
NameVersionClassification
PHENIX1.19_4092refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
XSCALEdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7K6R

7k6r


Resolution: 1.44→38.28 Å / SU ML: 0.13 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 16.69 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1881 1200 2.76 %
Rwork0.1655 42262 -
obs0.1661 43462 98.31 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 57.5 Å2 / Biso mean: 11.8094 Å2 / Biso min: 3.35 Å2
Refinement stepCycle: final / Resolution: 1.44→38.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1996 0 78 282 2356
Biso mean--15.33 19.66 -
Num. residues----242
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 (%)
1.44-1.50.26541250.22614393451892
1.5-1.560.18191330.172746964829100
1.56-1.650.17191320.157746714803100
1.65-1.750.17841350.164147234858100
1.75-1.880.2061340.16934735486999
1.88-2.070.17761350.15824747488299
2.07-2.370.17351330.15234695482899
2.37-2.990.18031350.17114776491199
2.99-38.280.19621380.16114826496497
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)
11.18390.66460.83990.6060.66525.5907-0.07370.14610.0402-0.22140.0557-0.0789-0.3580.13150.02380.09720.00560.01660.06980.00370.0938-5.16031.4736-9.9533
24.31233.7116-0.62166.0359-1.46731.54590.2273-0.2415-0.03990.4368-0.20910.01680.02160.0024-0.01430.07390.00450.00440.0811-0.00380.047-16.051-6.86669.7762
34.49921.078-1.77711.3179-0.39461.4997-0.00910.0449-0.1443-0.0037-0.0304-0.07250.06550.01440.0370.04140.0029-0.00060.0331-0.0040.055-13.7686-10.9029-0.5503
46.6496-1.53670.86326.7161-2.1327.12390.0980.1939-0.1491-0.2423-0.079-0.18230.13070.24180.00550.07-0.00580.01210.0492-0.02390.0675-5.297-8.8935-11.2624
51.65930.5288-0.94781.5897-0.28451.3550.01070.00170.056-0.05690.01460.0057-0.03770.0004-0.02870.02630.0099-0.01370.03520.00080.038-17.08341.1108-1.7867
66.1286-1.3471-0.90082.64010.70083.76580.09650.0934-0.3026-0.317-0.0337-0.06540.31070.1321-0.07350.15440.0035-0.01450.0963-0.00310.0496-16.809-0.4017-57.3447
72.09080.11930.93061.6594-1.96848.67990.02610.0015-0.0827-0.0510.08670.14150.0072-0.3628-0.12420.04380.0040.01090.0622-0.0040.0956-24.56433.3308-42.6239
83.32761.7244-0.37812.9194-0.13671.52250.1184-0.18080.11460.3101-0.09290.0262-0.15660.0062-0.01720.07030.0073-0.00030.0643-0.00190.063-8.938213.2099-31.9454
91.1977-0.08350.57091.0602-0.29110.9947-0.0124-0.00840.0196-0.03650.01160.01170.015-0.0350.00240.0354-0.00240.01580.0401-0.00330.0428-12.79665.3774-41.3927
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 2918 through 2945 )A0
2X-RAY DIFFRACTION2chain 'A' and (resid 2946 through 2963 )A0
3X-RAY DIFFRACTION3chain 'A' and (resid 2964 through 2982 )A0
4X-RAY DIFFRACTION4chain 'A' and (resid 2983 through 2988 )A0
5X-RAY DIFFRACTION5chain 'A' and (resid 2989 through 3036 )A0
6X-RAY DIFFRACTION6chain 'B' and (resid 2915 through 2929 )B0
7X-RAY DIFFRACTION7chain 'B' and (resid 2930 through 2945 )B0
8X-RAY DIFFRACTION8chain 'B' and (resid 2946 through 2973 )B0
9X-RAY DIFFRACTION9chain 'B' and (resid 2974 through 3037 )B0

+
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