[English] 日本語
Yorodumi
- PDB-6u5y: Discovery and optimization of salicyclic acid-derived sulfonamide... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6u5y
TitleDiscovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the WDR5:MYC protein-protein interaction
ComponentsWD repeat-containing protein 5
KeywordsTRANSCRIPTION / WDR5 / MYC / RBBP5 / structure-based design / high-throughput 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 ...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 / regulation of cell division / Formation of WDR5-containing histone-modifying complexes / MLL1 complex / regulation of embryonic development / 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. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. ...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. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Mainly Beta
Similarity search - Domain/homology
Chem-Q0M / WD repeat-containing protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.532 Å
AuthorsZhao, B. / Wang, F.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI) United States
CitationJournal: J.Med.Chem. / Year: 2019
Title: Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5-MYC Protein-Protein Interaction.
Authors: Macdonald, J.D. / Chacon Simon, S. / Han, C. / Wang, F. / Shaw, J.G. / Howes, J.E. / Sai, J. / Yuh, J.P. / Camper, D. / Alicie, B.M. / Alvarado, J. / Nikhar, S. / Payne, W. / Aho, E.R. / ...Authors: Macdonald, J.D. / Chacon Simon, S. / Han, C. / Wang, F. / Shaw, J.G. / Howes, J.E. / Sai, J. / Yuh, J.P. / Camper, D. / Alicie, B.M. / Alvarado, J. / Nikhar, S. / Payne, W. / Aho, E.R. / Bauer, J.A. / Zhao, B. / Phan, J. / Thomas, L.R. / Rossanese, O.W. / Tansey, W.P. / Waterson, A.G. / Stauffer, S.R. / Fesik, S.W.
History
DepositionAug 28, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 18, 2019Group: Database references / Category: citation / citation_author
Item: _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Jan 8, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Oct 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-containing protein 5
B: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,0144
Polymers66,9842
Non-polymers1,0302
Water14,448802
1
A: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,0072
Polymers33,4921
Non-polymers5151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,0072
Polymers33,4921
Non-polymers5151
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)99.021, 78.444, 80.199
Angle α, β, γ (deg.)90.000, 89.960, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-539-

HOH

21A-788-

HOH

31B-681-

HOH

41B-791-

HOH

-
Components

#1: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 33492.020 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P61964
#2: Chemical ChemComp-Q0M / 3-{[(5-bromo-3-chloro-2-hydroxyphenyl)sulfonyl]amino}-5-(1-cyanocyclobutyl)-2-hydroxy-N-methylbenzamide


Mass: 514.777 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H17BrClN3O5S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 802 / 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: 2.33 Å3/Da / Density % sol: 47.1 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: Bis-Tris pH 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: 0.9787 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Jul 19, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9787 Å / Relative weight: 1
ReflectionResolution: 1.53→40 Å / Num. obs: 92153 / % possible obs: 99 % / Redundancy: 5.1 % / CC1/2: 0.997 / Rmerge(I) obs: 0.08 / Rpim(I) all: 0.039 / Rrim(I) all: 0.092 / Rsym value: 0.084 / Net I/σ(I): 26.7
Reflection shellResolution: 1.53→1.56 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.554 / Mean I/σ(I) obs: 2.71 / Num. unique obs: 4150 / CC1/2: 0.704 / Rpim(I) all: 0.204 / Rrim(I) all: 0.398 / Rsym value: 0.339 / % possible all: 89.6

-
Processing

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

6dy7


Resolution: 1.532→28.711 Å / SU ML: 0.14 / Cross valid method: THROUGHOUT / σ(F): 1.45 / Phase error: 16.05 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1767 1985 2.17 %
Rwork0.1489 89493 -
obs0.1495 91478 99.38 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 57.86 Å2 / Biso mean: 16.1483 Å2 / Biso min: 6.06 Å2
Refinement stepCycle: final / Resolution: 1.532→28.711 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4679 0 60 802 5541
Biso mean--18.81 29.19 -
Num. residues----608
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.532-1.57030.23451390.2203628597
1.5703-1.61280.2261380.1977630699
1.6128-1.66020.16921430.178632099
1.6602-1.71380.21151380.1766634499
1.7138-1.77510.17821430.1646635499
1.7751-1.84610.2021420.1594638999
1.8461-1.93010.19111400.15276381100
1.9301-2.03180.19381400.15166378100
2.0318-2.15910.21821450.14686419100
2.1591-2.32570.18221430.14796430100
2.3257-2.55970.17981430.14626413100
2.5597-2.92970.14831470.14816434100
2.9297-3.68990.17751420.13446469100
3.6899-28.710.13211420.12696571100
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)
10.8230.1854-0.11710.9278-0.32840.98070.0885-0.2275-0.00620.1497-0.13470.0107-0.01180.07260.05030.1137-0.04150.00160.1342-0.01060.067-13.853412.470715.5892
20.9820.28520.71041.38810.82021.8792-0.1085-0.01390.1151-0.06190.03680.0693-0.14860.09930.0740.077-0.0057-0.01450.0643-0.01170.0763-16.112622.52121.2609
32.02980.63770.48551.73790.80712.4024-0.06080.1042-0.0371-0.10830.0793-0.0723-0.01720.1044-0.05220.08990-0.00110.03610.01290.0714-16.451810.9834-9.2501
41.15950.1547-0.2550.82620.24931.6439-0.0158-0.0286-0.0853-0.0069-0.0325-0.03850.05660.05140.05230.0835-0.0053-0.00190.0460.02140.0856-17.222-1.51655.634
50.92540.21910.1480.93070.29751.18290.0968-0.2790.02910.1918-0.12690.01430.0283-0.12020.05070.1309-0.0564-0.01190.1777-0.00320.0757-35.62753.206958.3069
60.98220.2176-0.87611.2151-0.52721.6466-0.086-0.0423-0.1185-0.0401-0.0105-0.08270.1216-0.03930.080.0718-0.0096-0.00670.07240.01760.0773-33.6716-8.67943.2369
71.91070.6358-0.67671.6481-0.82042.4377-0.06560.09390.0209-0.11670.07950.09070.0153-0.136-0.060.0926-0.0006-0.01110.0412-0.01130.0751-33.04352.126530.8498
81.16820.13670.18270.7889-0.25341.5844-0.0188-0.01510.0726-0.0209-0.02990.0393-0.0538-0.05420.04810.0839-0.0068-0.00730.0458-0.02420.0851-32.048814.472645.686
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 31 through 106 )A31 - 106
2X-RAY DIFFRACTION2chain 'A' and (resid 107 through 167 )A107 - 167
3X-RAY DIFFRACTION3chain 'A' and (resid 168 through 209 )A168 - 209
4X-RAY DIFFRACTION4chain 'A' and (resid 210 through 334 )A210 - 334
5X-RAY DIFFRACTION5chain 'B' and (resid 31 through 84 )B31 - 84
6X-RAY DIFFRACTION6chain 'B' and (resid 85 through 167 )B85 - 167
7X-RAY DIFFRACTION7chain 'B' and (resid 168 through 209 )B168 - 209
8X-RAY DIFFRACTION8chain 'B' and (resid 210 through 334 )B210 - 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://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