+Open data
-Basic information
Entry | Database: PDB / ID: 6g5w | ||||||
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Title | Crystal Structure of KDM4A with compound YP-03-038 | ||||||
Components | Lysine-specific demethylase 4A | ||||||
Keywords | OXIDOREDUCTASE / KDM4A / ligand binding / drug design / inhibitor design / cancer / epigenetics / JMJD2A | ||||||
Function / homology | Function and homology information [histone H3]-trimethyl-L-lysine36 demethylase / histone H3K36me2/H3K36me3 demethylase activity / apoptotic chromosome condensation / histone H3K36 demethylase activity / cardiac muscle hypertrophy in response to stress / histone H3K9me2/H3K9me3 demethylase activity / [histone H3]-trimethyl-L-lysine9 demethylase / histone H3K9 demethylase activity / negative regulation of astrocyte differentiation / histone demethylase activity ...[histone H3]-trimethyl-L-lysine36 demethylase / histone H3K36me2/H3K36me3 demethylase activity / apoptotic chromosome condensation / histone H3K36 demethylase activity / cardiac muscle hypertrophy in response to stress / histone H3K9me2/H3K9me3 demethylase activity / [histone H3]-trimethyl-L-lysine9 demethylase / histone H3K9 demethylase activity / negative regulation of astrocyte differentiation / histone demethylase activity / pericentric heterochromatin / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / methylated histone binding / positive regulation of neuron differentiation / response to nutrient levels / negative regulation of autophagy / HDMs demethylate histones / fibrillar center / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / regulation of gene expression / chromatin remodeling / negative regulation of gene expression / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / positive regulation of gene expression / chromatin / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.83 Å | ||||||
Authors | Malecki, P.H. / Carter, D.M. / Gohlke, U. / Specker, E. / Nazare, M. / Weiss, M.S. / Heinemann, U. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer. Authors: Carter, D.M. / Specker, E. / Malecki, P.H. / Przygodda, J. / Dudaniec, K. / Weiss, M.S. / Heinemann, U. / Nazare, M. / Gohlke, U. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6g5w.cif.gz | 320.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6g5w.ent.gz | 260.5 KB | Display | PDB format |
PDBx/mmJSON format | 6g5w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6g5w_validation.pdf.gz | 819.5 KB | Display | wwPDB validaton report |
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Full document | 6g5w_full_validation.pdf.gz | 827.5 KB | Display | |
Data in XML | 6g5w_validation.xml.gz | 31.9 KB | Display | |
Data in CIF | 6g5w_validation.cif.gz | 46.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g5/6g5w ftp://data.pdbj.org/pub/pdb/validation_reports/g5/6g5w | HTTPS FTP |
-Related structure data
Related structure data | 6g5xC 3pdqS 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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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 41767.543 Da / Num. of mol.: 2 / Fragment: JMJD2A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KDM4A, JHDM3A, JMJD2, JMJD2A, KIAA0677 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: O75164, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor |
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-Non-polymers , 7 types, 450 molecules
#2: Chemical | #3: Chemical | ChemComp-NI / #4: Chemical | #5: Chemical | #6: Chemical | ChemComp-NA / | #7: Chemical | ChemComp-ENZ / ( | #8: 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: 2.49 Å3/Da / Density % sol: 50.63 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion / pH: 5.5 / Details: 100mM Citrate, 10mM NiCl2, 20% PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.9184 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 4, 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: DOUBLE CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9184 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.83→46.571 Å / Num. obs: 74525 / % possible obs: 99.5 % / Redundancy: 5.808 % / Biso Wilson estimate: 30.82 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.061 / Rrim(I) all: 0.068 / Χ2: 0.994 / Net I/σ(I): 15.78 / Num. measured all: 432868 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3PDQ Resolution: 1.83→46.571 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 23.35
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 175.04 Å2 / Biso mean: 44.6793 Å2 / Biso min: 19.31 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.83→46.571 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15
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Refinement TLS params. | Method: refined / Origin x: 34.1206 Å / Origin y: 37.8913 Å / Origin z: 18.2426 Å
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Refinement TLS group |
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