+Open data
-Basic information
Entry | Database: PDB / ID: 4ekg | ||||||
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Title | Crystal Structure of DOT1L in Complex with EPZ003696 | ||||||
Components | Histone-lysine N-methyltransferase, H3 lysine-79 specific | ||||||
Keywords | transferase/transferase inhibitor / methyltransferase / transferase-transferase inhibitor complex | ||||||
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: 2.8 Å | ||||||
Authors | Jin, L. | ||||||
Citation | Journal: Chem.Biol.Drug Des. / Year: 2012 Title: Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L. Authors: Basavapathruni, A. / Jin, L. / Daigle, S.R. / Majer, C.R. / Therkelsen, C.A. / Wigle, T.J. / Kuntz, K.W. / Chesworth, R. / Pollock, R.M. / Scott, M.P. / Moyer, M.P. / Richon, V.M. / Copeland, R.A. / Olhava, E.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ekg.cif.gz | 81.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ekg.ent.gz | 59.8 KB | Display | PDB format |
PDBx/mmJSON format | 4ekg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4ekg_validation.pdf.gz | 703.2 KB | Display | wwPDB validaton report |
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Full document | 4ekg_full_validation.pdf.gz | 705.7 KB | Display | |
Data in XML | 4ekg_validation.xml.gz | 13.9 KB | Display | |
Data in CIF | 4ekg_validation.cif.gz | 18.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ek/4ekg ftp://data.pdbj.org/pub/pdb/validation_reports/ek/4ekg | HTTPS FTP |
-Related structure data
Related structure data | 4ek9C 4ekiC 3qowS 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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Unit cell |
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-Components
#1: Protein | Mass: 48566.234 Da / Num. of mol.: 1 / Fragment: UNP residues 1-416 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 |
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#2: Chemical | ChemComp-0QJ / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.63 Å3/Da / Density % sol: 66.1 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.2 Details: 100 mM Sodium Acetate, 1.8-2.0 M Ammonium Sulfate, 5 mM TCEP, pH 5.2, soaking the compound into cross-linked DOT1L-SAM crystal, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 10, 2009 |
Radiation | Monochromator: SI 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
Reflection | Resolution: 2.8→41.7 Å / Num. all: 17520 / Num. obs: 17520 / % possible obs: 100 % / Observed criterion σ(I): 1 / Redundancy: 6.1 % / Rmerge(I) obs: 0.094 / Net I/σ(I): 11.8 |
Reflection shell | Resolution: 2.8→2.95 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.421 / Mean I/σ(I) obs: 3.5 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3QOW Resolution: 2.8→41.7 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.897 / SU B: 10.492 / SU ML: 0.209 / Cross valid method: THROUGHOUT / ESU R: 0.396 / ESU R Free: 0.297 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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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: 74.056 Å2
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Refinement step | Cycle: LAST / Resolution: 2.8→41.7 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.801→2.874 Å / Total num. of bins used: 20
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