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Yorodumi- PDB-5dt2: Crystal structure of Dot1L in complex with inhibitor CPD11 [N4-me... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5dt2 | ||||||
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Title | Crystal structure of Dot1L in complex with inhibitor CPD11 [N4-methyl-N2-(2-methyl-1-(2-phenoxyphenyl)-1H-indol-6-yl)pyrimidine-2,4-diamine] | ||||||
Components | Histone-lysine N-methyltransferase, H3 lysine-79 specific | ||||||
Keywords | TRANSFERASE / Inhibitor / Complex / Methyltransferase | ||||||
Function / homology | Function and homology information histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / telomere organization / DNA damage checkpoint signaling ...histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / telomere organization / DNA damage checkpoint signaling / PKMTs methylate histone lysines / gene expression / methylation / RNA polymerase II-specific DNA-binding transcription factor binding / nucleic acid binding / transcription coactivator activity / intracellular membrane-bounded organelle / DNA repair / positive regulation of cell population proliferation / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / nucleoplasm / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Scheufler, C. / Gaul, C. / Be, C. / Moebitz, H. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2016 Title: Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach. Authors: Chen, C. / Zhu, H. / Stauffer, F. / Caravatti, G. / Vollmer, S. / Machauer, R. / Holzer, P. / Mobitz, H. / Scheufler, C. / Klumpp, M. / Tiedt, R. / Beyer, K.S. / Calkins, K. / Guthy, D. / ...Authors: Chen, C. / Zhu, H. / Stauffer, F. / Caravatti, G. / Vollmer, S. / Machauer, R. / Holzer, P. / Mobitz, H. / Scheufler, C. / Klumpp, M. / Tiedt, R. / Beyer, K.S. / Calkins, K. / Guthy, D. / Kiffe, M. / Zhang, J. / Gaul, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5dt2.cif.gz | 271.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5dt2.ent.gz | 220.3 KB | Display | PDB format |
PDBx/mmJSON format | 5dt2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5dt2_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 5dt2_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5dt2_validation.xml.gz | 26.7 KB | Display | |
Data in CIF | 5dt2_validation.cif.gz | 37.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dt/5dt2 ftp://data.pdbj.org/pub/pdb/validation_reports/dt/5dt2 | HTTPS FTP |
-Related structure data
Related structure data | 5drtC 5dryC 5dsxC 1nw3S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 38456.594 Da / Num. of mol.: 2 / Fragment: UNP residues 2-332 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DOT1L, KIAA1814, KMT4 / Production host: Escherichia coli (E. coli) References: UniProt: Q8TEK3, histone-lysine N-methyltransferase #2: Chemical | #3: Chemical | ChemComp-SO4 / #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.51 Å3/Da / Density % sol: 64.93 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion Details: 1.4M lithium sulfate 0.1M sodium citrate tribasic dihydrate 0.3M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99998 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Jun 16, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99998 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. obs: 47515 / % possible obs: 100 % / Redundancy: 10.2 % / Biso Wilson estimate: 49.9 Å2 / Rmerge(I) obs: 0.108 / Net I/σ(I): 15.82 |
Reflection shell | Resolution: 2.3→2.36 Å / Redundancy: 9.4 % / Rmerge(I) obs: 1.177 / Mean I/σ(I) obs: 2.33 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1nw3 Resolution: 2.3→45.7 Å / Cor.coef. Fo:Fc: 0.9402 / Cor.coef. Fo:Fc free: 0.9217 / SU R Cruickshank DPI: 0.19 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.188 / SU Rfree Blow DPI: 0.161 / SU Rfree Cruickshank DPI: 0.164
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Displacement parameters | Biso mean: 58.16 Å2
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Refine analyze | Luzzati coordinate error obs: 0.328 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.3→45.7 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.36 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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