[English] 日本語
Yorodumi
- PDB-6uik: Discovery of fragment-inspired heterocyclic benzenesulfonmides as... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6uik
TitleDiscovery of fragment-inspired heterocyclic benzenesulfonmides as inhibitors of the WDR5-MYC interaction
ComponentsWD repeat domanin 5
KeywordsTRANSCRIPTION / WDR5 / MYC / structure-based design / fragment screening
Function / homology
Function and homology information


MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes ...MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / regulation of embryonic development / MLL1 complex / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / histone acetyltransferase complex / positive regulation of gluconeogenesis / transcription initiation-coupled chromatin remodeling / methylated histone binding / skeletal system development / gluconeogenesis / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / mitotic spindle / PKMTs methylate histone lysines / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Neddylation / HATs acetylate histones / histone binding / regulation of cell cycle / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / nucleoplasm / nucleus
Similarity search - Function
YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats ...YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Mainly Beta
Similarity search - Domain/homology
Chem-Q8M / WD repeat-containing protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsZhao, B.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery of WD Repeat-Containing Protein 5 (WDR5)-MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design.
Authors: Chacon Simon, S. / Wang, F. / Thomas, L.R. / Phan, J. / Zhao, B. / Olejniczak, E.T. / Macdonald, J.D. / Shaw, J.G. / Schlund, C. / Payne, W. / Creighton, J. / Stauffer, S.R. / Waterson, A.G. ...Authors: Chacon Simon, S. / Wang, F. / Thomas, L.R. / Phan, J. / Zhao, B. / Olejniczak, E.T. / Macdonald, J.D. / Shaw, J.G. / Schlund, C. / Payne, W. / Creighton, J. / Stauffer, S.R. / Waterson, A.G. / Tansey, W.P. / Fesik, S.W.
History
DepositionOct 1, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 15, 2020Provider: repository / Type: Initial release
Revision 1.1May 6, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Oct 11, 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: WD repeat domanin 5
B: WD repeat domanin 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,8254
Polymers66,9842
Non-polymers8412
Water14,196788
1
A: WD repeat domanin 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,9132
Polymers33,4921
Non-polymers4211
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: WD repeat domanin 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,9132
Polymers33,4921
Non-polymers4211
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)134.263, 46.880, 112.842
Angle α, β, γ (deg.)90.000, 117.390, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein WD repeat domanin 5


Mass: 33492.020 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P61964
#2: Chemical ChemComp-Q8M / 5-bromo-3-chloro-N-(1-cyclopentyl-1H-imidazol-4-yl)-2-hydroxybenzene-1-sulfonamide


Mass: 420.709 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H15BrClN3O3S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 788 / 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: 47.74 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / Details: Bis-Tris 6.5, 0.2 M Ammonium Acetate, 28% PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.978 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Mar 23, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.978 Å / Relative weight: 1
ReflectionResolution: 1.6→40 Å / Num. obs: 80531 / % possible obs: 97.5 % / Redundancy: 6.6 % / CC1/2: 0.997 / Rmerge(I) obs: 0.056 / Rpim(I) all: 0.025 / Rrim(I) all: 0.066 / Rsym value: 0.061 / Net I/σ(I): 43.1
Reflection shellResolution: 1.6→1.63 Å / Rmerge(I) obs: 0.22 / Mean I/σ(I) obs: 8.6 / Num. unique obs: 3949 / CC1/2: 0.97 / Rpim(I) all: 0.089 / Rrim(I) all: 0.224 / Rsym value: 0.205 / % possible all: 95.9

-
Processing

Software
NameVersionClassification
PHENIX1.15.2_3472refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6DY7

6dy7


Resolution: 1.6→28.979 Å / SU ML: 0.13 / Cross valid method: THROUGHOUT / σ(F): 1.46 / Phase error: 17.15 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1825 1999 2.48 %
Rwork0.1592 78496 -
obs0.1598 80495 97.37 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 65.63 Å2 / Biso mean: 18.8052 Å2 / Biso min: 5.59 Å2
Refinement stepCycle: final / Resolution: 1.6→28.979 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4662 0 46 788 5496
Biso mean--27.48 31.94 -
Num. residues----607
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.6001-1.64010.21291380.166539494
1.6401-1.68440.19681400.1634550596
1.6844-1.7340.19381410.1585556196
1.734-1.790.18551390.1568547797
1.79-1.85390.19971410.1557552897
1.8539-1.92810.19081420.1557558797
1.9281-2.01590.1931420.1519556797
2.0159-2.12210.17521430.1584561998
2.1221-2.2550.17151440.1618562498
2.255-2.42910.17831420.1653563498
2.4291-2.67330.1891460.1712567698
2.6733-3.05980.17811440.169570799
3.0598-3.85360.18681480.1521576099
3.8536-28.970.16571490.1531585798
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)
11.21460.00590.15640.628-0.41011.3772-0.06390.08780.2515-0.02420.01250.0694-0.2492-0.02630.00680.13720.0019-0.03430.05770.01130.1381127.208322.207234.6343
22.3518-0.50140.59491.6833-0.62062.0692-0.0512-0.32810.15740.02540.0550.2285-0.1625-0.3336-0.0240.10650.01810.00540.1237-0.01470.1126121.829114.668846.669
32.0546-0.24090.48251.2557-0.13211.9994-0.0062-0.0368-0.21530.0258-0.01510.04970.17470.01210.01160.0984-0.00020.00820.04010.00860.1052131.35933.690642.3862
43.86281.52490.56531.6108-0.03951.99780.04440.093-0.4819-0.0334-0.0053-0.05310.41680.19540.04230.21580.0509-0.01020.0828-0.01270.196138.9966-3.551338.3074
53.41840.40240.49672.19850.3382.33070.03630.2683-0.3752-0.19780.0219-0.21680.21320.3729-0.05010.13610.03180.01710.1574-0.01020.1443143.16743.933530.6794
63.0954-0.0480.91031.0606-0.33942.0297-0.00490.2695-0.011-0.1043-0.1006-0.11870.03560.33310.13730.0860.01510.02080.20150.02590.1101144.198311.435426.9629
72.6839-0.15550.63821.1807-0.38872.0033-0.1690.52460.5511-0.1728-0.0886-0.213-0.2260.37030.0630.1309-0.0367-0.01240.28750.10260.1811144.403719.73421.6132
83.01340.13580.36041.0556-0.74090.7259-0.29940.10060.71660.03330.0764-0.1196-0.34630.18540.23740.15320.0091-0.06640.12460.00380.2306134.259823.968126.4964
91.02310.2594-0.19970.88070.13840.94640.0277-0.0975-0.09540.0202-0.0554-0.1184-0.04670.09760.02590.0661-0.0094-0.00230.07460.03890.0904113.8355-8.361911.7682
100.5322-0.75890.32131.98630.23831.6097-0.0636-0.2396-0.44890.0243-0.06490.070.2006-0.13610.02490.1076-0.02410.03910.1260.05740.2181100.8814-21.804516.1598
112.03860.574-0.15660.95650.05421.12250.1267-0.3031-0.01030.1861-0.18560.0564-0.0363-0.04950.02060.1092-0.04380.01940.17430.02670.0672100.0697-5.49224.2624
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 32 through 106 )A32 - 106
2X-RAY DIFFRACTION2chain 'A' and (resid 107 through 126 )A107 - 126
3X-RAY DIFFRACTION3chain 'A' and (resid 127 through 190 )A127 - 190
4X-RAY DIFFRACTION4chain 'A' and (resid 191 through 209 )A191 - 209
5X-RAY DIFFRACTION5chain 'A' and (resid 210 through 233 )A210 - 233
6X-RAY DIFFRACTION6chain 'A' and (resid 234 through 282 )A234 - 282
7X-RAY DIFFRACTION7chain 'A' and (resid 283 through 303 )A283 - 303
8X-RAY DIFFRACTION8chain 'A' and (resid 304 through 334 )A304 - 334
9X-RAY DIFFRACTION9chain 'B' and (resid 31 through 190 )B31 - 190
10X-RAY DIFFRACTION10chain 'B' and (resid 191 through 233 )B191 - 233
11X-RAY DIFFRACTION11chain 'B' and (resid 234 through 334 )B234 - 334

+
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