[English] 日本語
Yorodumi
- PDB-6ujj: Discovery of fragment-inspired heterocyclic benzenesulfonamides a... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ujj
TitleDiscovery of fragment-inspired heterocyclic benzenesulfonamides as inhibitors of the WDR5-MYC interaction
ComponentsWD repeat-containing protein 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 ...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
5-[4-(trifluoromethyl)phenyl]-1H-tetrazole / WD repeat-containing protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.731 Å
AuthorsPhan, J.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) 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 3, 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-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,6052
Polymers34,3911
Non-polymers2141
Water5,260292
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)81.482, 86.534, 39.746
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Components on special symmetry positions
IDModelComponents
11A-765-

HOH

-
Components

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


Mass: 34390.992 Da / Num. of mol.: 1
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-QBP / 5-[4-(trifluoromethyl)phenyl]-1H-tetrazole


Mass: 214.147 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H5F3N4 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 292 / 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: 2.04 Å3/Da / Density % sol: 39.62 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1 M Hepes, 0.2 M ammonium acetate, 32% PEG3350 / PH range: 7.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 1 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 12, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.73→50 Å / Num. obs: 29896 / % possible obs: 99.8 % / Redundancy: 7.6 % / Rmerge(I) obs: 0.061 / Rpim(I) all: 0.023 / Rrim(I) all: 0.065 / Χ2: 0.987 / Net I/σ(I): 22.88
Reflection shellResolution: 1.73→1.76 Å / Redundancy: 7.5 % / Rmerge(I) obs: 0.68 / Mean I/σ(I) obs: 3.48 / Num. unique obs: 1446 / Rpim(I) all: 0.258 / Rrim(I) all: 0.729 / Χ2: 1.09 / % possible all: 99.4

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
PHENIXdev_1839refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4Y7R

4y7r


Resolution: 1.731→38.214 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 19.21
RfactorNum. reflection% reflection
Rfree0.1895 1510 5.06 %
Rwork0.1553 --
obs0.157 29845 99.34 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 93.45 Å2 / Biso mean: 29.3612 Å2 / Biso min: 12.45 Å2
Refinement stepCycle: final / Resolution: 1.731→38.214 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2364 0 15 292 2671
Biso mean--75.34 37.59 -
Num. residues----305
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0082467
X-RAY DIFFRACTIONf_angle_d1.0753356
X-RAY DIFFRACTIONf_chiral_restr0.05378
X-RAY DIFFRACTIONf_plane_restr0.005416
X-RAY DIFFRACTIONf_dihedral_angle_d11.812878
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.7311-1.7870.26421370.2064238395
1.787-1.85080.23161420.19082530100
1.8508-1.92490.20821470.17272537100
1.9249-2.01250.20671220.16192573100
2.0125-2.11860.19621300.16162558100
2.1186-2.25130.20871110.16212587100
2.2513-2.42510.22481260.17042591100
2.4251-2.66910.22311630.17752585100
2.6691-3.05520.18651660.16752588100
3.0552-3.84870.17051390.14812624100
3.8487-4.64220.15351270.1282277999
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)
12.29070.2405-0.31351.4474-0.87511.22670.05910.1436-0.1729-0.0393-0.0467-0.20230.08480.1959-0.00360.1761-0.0014-0.01910.1869-0.03690.1774-0.288625.7228-11.404
23.16170.5628-0.08711.43550.14291.13590.0729-0.10560.44590.07820.01940.1105-0.1117-0.085-0.06510.1821-0.01830.00580.1307-0.0190.1983-16.015736.9815-8.4738
32.07960.3869-0.40761.7394-0.75841.8814-0.124-0.0013-0.08-0.02350.15970.19530.0258-0.1913-0.03660.1737-0.03130.01570.2486-0.00130.1661-27.816125.0208-7.3167
42.8982-0.74390.53931.7088-0.12831.32280.0058-0.2082-0.9816-0.04130.18040.2530.2899-0.3048-0.06530.2302-0.03920.01060.20180.03060.3657-18.35613.138-6.5233
51.65510.12410.05961.2068-0.07112.13880.01770.091-0.7166-0.11440.03860.11370.30220.2199-0.04360.19760.0421-0.02540.1202-0.06490.3164-3.960313.8005-9.0587
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 30 through 83 )A30 - 83
2X-RAY DIFFRACTION2chain 'A' and (resid 84 through 167 )A84 - 167
3X-RAY DIFFRACTION3chain 'A' and (resid 168 through 209 )A168 - 209
4X-RAY DIFFRACTION4chain 'A' and (resid 210 through 282 )A210 - 282
5X-RAY DIFFRACTION5chain 'A' and (resid 283 through 334 )A283 - 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