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Yorodumi- PDB-6te1: Structure of the KDM1A/CoREST complex with the inhibitor 2-[3-{4-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6te1 | ||||||
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Title | Structure of the KDM1A/CoREST complex with the inhibitor 2-[3-{4-chloro-3-[(4-chlorophenyl)ethynyl]phenyl}-1-(3-morpholin-4-ylpropyl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-oxoethanol | ||||||
Components |
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Keywords | OXIDOREDUCTASE / HISTONE DEMETHYLASE / INHIBITOR / COMPLEX | ||||||
Function / homology | Function and homology information positive regulation of megakaryocyte differentiation / guanine metabolic process / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / protein demethylation / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity / telomeric repeat-containing RNA binding / regulation of DNA methylation-dependent heterochromatin formation / muscle cell development / histone H3K4 demethylase activity ...positive regulation of megakaryocyte differentiation / guanine metabolic process / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / protein demethylation / FAD-dependent H3K4me/H3K4me3 demethylase activity / demethylase activity / telomeric repeat-containing RNA binding / regulation of DNA methylation-dependent heterochromatin formation / muscle cell development / histone H3K4 demethylase activity / positive regulation of neural precursor cell proliferation / neuron maturation / MRF binding / regulation of androgen receptor signaling pathway / DNA repair complex / DNA repair-dependent chromatin remodeling / nuclear androgen receptor binding / regulation of double-strand break repair via homologous recombination / positive regulation of neuroblast proliferation / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of stem cell proliferation / negative regulation of DNA binding / histone H3K9 demethylase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / histone deacetylase complex / positive regulation of cell size / histone demethylase activity / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / response to fungicide / cellular response to cAMP / transcription repressor complex / erythrocyte differentiation / nuclear receptor coactivator activity / negative regulation of protein binding / Regulation of PTEN gene transcription / positive regulation of protein ubiquitination / promoter-specific chromatin binding / HDACs deacetylate histones / cellular response to gamma radiation / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / HDMs demethylate histones / negative regulation of DNA-binding transcription factor activity / positive regulation of neuron projection development / cerebral cortex development / transcription corepressor activity / cellular response to UV / regulation of protein localization / p53 binding / flavin adenine dinucleotide binding / chromatin organization / positive regulation of cold-induced thermogenesis / Factors involved in megakaryocyte development and platelet production / DNA-binding transcription factor binding / Estrogen-dependent gene expression / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / chromosome, telomeric region / transcription coactivator activity / oxidoreductase activity / negative regulation of gene expression / negative regulation of DNA-templated transcription / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / nucleus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.11 Å | ||||||
Authors | Pasqualato, S. / Cecatiello, V. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2020 Title: Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models. Authors: Romussi, A. / Cappa, A. / Vianello, P. / Brambillasca, S. / Cera, M.R. / Dal Zuffo, R. / Faga, G. / Fattori, R. / Moretti, L. / Trifiro, P. / Villa, M. / Vultaggio, S. / Cecatiello, V. / ...Authors: Romussi, A. / Cappa, A. / Vianello, P. / Brambillasca, S. / Cera, M.R. / Dal Zuffo, R. / Faga, G. / Fattori, R. / Moretti, L. / Trifiro, P. / Villa, M. / Vultaggio, S. / Cecatiello, V. / Pasqualato, S. / Dondio, G. / So, C.W.E. / Minucci, S. / Sartori, L. / Varasi, M. / Mercurio, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6te1.cif.gz | 365 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6te1.ent.gz | 280.1 KB | Display | PDB format |
PDBx/mmJSON format | 6te1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/te/6te1 ftp://data.pdbj.org/pub/pdb/validation_reports/te/6te1 | HTTPS FTP |
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-Related structure data
Related structure data | 5lhgS S: Starting model for refinement |
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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
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 93011.453 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KDM1A, AOF2, KDM1, KIAA0601, LSD1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60341, Oxidoreductases |
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#2: Protein | Mass: 53101.961 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RCOR1, KIAA0071, RCOR / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UKL0 |
-Non-polymers , 4 types, 22 molecules
#3: Chemical | #4: Chemical | ChemComp-FAD / | #5: Chemical | ChemComp-GOL / #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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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: 4.38 Å3/Da / Density % sol: 71.92 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6 / Details: 1.1-1.2 M NA/K TARTRATE 0.1 M ADA |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1.00001 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 14, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.00001 Å / Relative weight: 1 |
Reflection | Resolution: 3.11→46.23 Å / Num. obs: 46368 / % possible obs: 99.8 % / Redundancy: 5.5 % / Biso Wilson estimate: 71.56 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.081 / Rpim(I) all: 0.04 / Rrim(I) all: 0.096 / Net I/σ(I): 14.7 |
Reflection shell | Resolution: 3.11→3.19 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.806 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 3413 / CC1/2: 0.75 / Rpim(I) all: 0.394 / Rrim(I) all: 0.976 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5LHG Resolution: 3.11→46.05 Å / Cross valid method: FREE R-VALUE
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Displacement parameters | Biso mean: 91.46 Å2 | ||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.11→46.05 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.11→3.221 Å
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