[English] 日本語
Yorodumi- PDB-8g3c: Crystal structure of human WDR5 in complex with N-[(2'-cyano[1,1'... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8g3c | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of human WDR5 in complex with N-[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]-3-hydroxy-6-methyl-4-oxo-4H-pyran-2-carboxamide (compound 1, WDR5-MYC PPI inhibitor) | ||||||
Components | WD repeat-containing protein 5 | ||||||
Keywords | ONCOPROTEIN/INHIBITOR / WDR5 / WBM / MYC / small molecule / ONCOPROTEIN-INHIBITOR complex | ||||||
Function / homology | Function and homology information MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / regulation of tubulin deacetylation / histone methyltransferase complex / 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 / regulation of tubulin deacetylation / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / regulation of embryonic development / MLL1 complex / histone acetyltransferase complex / positive regulation of gluconeogenesis / methylated histone binding / transcription initiation-coupled chromatin remodeling / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å | ||||||
Authors | Zhao, M. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: J.Med.Chem. / Year: 2023 Title: Discovery and Structure-Based Design of Inhibitors of the WD Repeat-Containing Protein 5 (WDR5)-MYC Interaction. Authors: Ding, J. / Liu, L. / Chiang, Y.L. / Zhao, M. / Liu, H. / Yang, F. / Shen, L. / Lin, Y. / Deng, H. / Gao, J. / Sage, D.R. / West, L. / Llamas, L.A. / Hao, X. / Kawatkar, S. / Li, E. / Jain, R. ...Authors: Ding, J. / Liu, L. / Chiang, Y.L. / Zhao, M. / Liu, H. / Yang, F. / Shen, L. / Lin, Y. / Deng, H. / Gao, J. / Sage, D.R. / West, L. / Llamas, L.A. / Hao, X. / Kawatkar, S. / Li, E. / Jain, R.K. / Tallarico, J.A. / Canham, S.M. / Wang, H. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8g3c.cif.gz | 78.9 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8g3c.ent.gz | 55.2 KB | Display | PDB format |
PDBx/mmJSON format | 8g3c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g3/8g3c ftp://data.pdbj.org/pub/pdb/validation_reports/g3/8g3c | HTTPS FTP |
---|
-Related structure data
Related structure data | 8g3eC 8f1gS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: 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 (E. coli) / References: UniProt: P61964 |
---|---|
#2: Chemical | ChemComp-YJN / |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.36 Å3/Da / Density % sol: 47.92 % |
---|---|
Crystal grow | Temperature: 294 K / Method: vapor diffusion, sitting drop / Details: 20% PEG3350, 0.2 M potassium acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.97919 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 12, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97919 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→50 Å / Num. obs: 30595 / % possible obs: 98.8 % / Redundancy: 12.8 % / Rmerge(I) obs: 0.157 / Net I/σ(I): 11.9 |
Reflection shell | Resolution: 1.8→1.84 Å / Rmerge(I) obs: 1.003 / Num. unique obs: 2152 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 8F1G Resolution: 1.8→40.76 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.939 / SU B: 2.779 / SU ML: 0.085 / Cross valid method: THROUGHOUT / ESU R: 0.138 / ESU R Free: 0.122 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 23.761 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 1.8→40.76 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
|