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Yorodumi- PDB-5mw3: Crystal structure of Dot1L in complex with inhibitor CPD1 [N6-(2,... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5mw3 | ||||||
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Title | Crystal structure of Dot1L in complex with inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine] and inhibitor CPD2 [(R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine] | ||||||
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 / telomere organization / DNA damage checkpoint signaling / heterochromatin formation ...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 / telomere organization / DNA damage checkpoint signaling / heterochromatin formation / 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: 2.09 Å | ||||||
Authors | Be, C. / Koch, E. / Gaul, C. / Stauffer, F. / Moebitz, H. / Scheufler, C. | ||||||
Citation | Journal: ACS Med Chem Lett / Year: 2017 Title: Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. Authors: Mobitz, H. / Machauer, R. / Holzer, P. / Vaupel, A. / Stauffer, F. / Ragot, C. / Caravatti, G. / Scheufler, C. / Fernandez, C. / Hommel, U. / Tiedt, R. / Beyer, K.S. / Chen, C. / Zhu, H. / Gaul, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5mw3.cif.gz | 278.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5mw3.ent.gz | 225.6 KB | Display | PDB format |
PDBx/mmJSON format | 5mw3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mw/5mw3 ftp://data.pdbj.org/pub/pdb/validation_reports/mw/5mw3 | HTTPS FTP |
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-Related structure data
Related structure data | 5mvsC 5mw4C 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 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 | #4: Chemical | ChemComp-TLA / | #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.49 Å3/Da / Density % sol: 64.77 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / Details: 1.4M K/Na tartrate, 0.1M Hepes pH6.6 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 12, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.09→50 Å / Num. all: 62942 / Num. obs: 62901 / % possible obs: 99.9 % / Redundancy: 10.2 % / Biso Wilson estimate: 35.17 Å2 / Rsym value: 0.112 / Net I/σ(I): 15.46 |
Reflection shell | Resolution: 2.09→2.14 Å / Redundancy: 9.6 % / Mean I/σ(I) obs: 2.51 / % possible all: 99.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1nw3 Resolution: 2.09→45.75 Å / Cor.coef. Fo:Fc: 0.9491 / Cor.coef. Fo:Fc free: 0.9457 / SU R Cruickshank DPI: 0.135 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.136 / SU Rfree Blow DPI: 0.119 / SU Rfree Cruickshank DPI: 0.12
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Displacement parameters | Biso mean: 43.82 Å2
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Refine analyze | Luzzati coordinate error obs: 0.271 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.09→45.75 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.09→2.14 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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