+Open data
-Basic information
Entry | Database: PDB / ID: 6s35 | |||||||||
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Title | LSD1/CoREST1 complex with macrocyclic peptide inhibitor | |||||||||
Components |
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Keywords | FLAVOPROTEIN / 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) synthetic construct (others) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.1 Å | |||||||||
Authors | Talibov, V.O. / Dobritzsch, D. | |||||||||
Funding support | Sweden, 2items
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Citation | Journal: Acs Omega / Year: 2020 Title: Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1. Authors: Yang, J. / Talibov, V.O. / Peintner, S. / Rhee, C. / Poongavanam, V. / Geitmann, M. / Sebastiano, M.R. / Simon, B. / Hennig, J. / Dobritzsch, D. / Danielson, U.H. / Kihlberg, J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6s35.cif.gz | 339.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6s35.ent.gz | 277.4 KB | Display | PDB format |
PDBx/mmJSON format | 6s35.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/s3/6s35 ftp://data.pdbj.org/pub/pdb/validation_reports/s3/6s35 | HTTPS FTP |
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-Related structure data
Related structure data | 2v1dS 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
#1: Protein | Mass: 74065.711 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 / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 / References: UniProt: O60341, Oxidoreductases |
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#2: Protein | Mass: 20658.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RCOR1, KIAA0071, RCOR / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta 2 / References: UniProt: Q9UKL0 |
#3: Protein/peptide | Mass: 1308.531 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: Side chains amide bridge between D-Lys3 and Glu6 / Source: (synth.) synthetic construct (others) |
#4: Chemical | ChemComp-FAD / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 6.6 Å3/Da |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: Crystallization: hanging drop, 2 uL total, 1:1 protein-to-reservoir. Protein: 11 mg/mL in 50 mM HEPES, 200 mM NaCl, 2 mM DTT, pH 7.5. Reservoir: 100 mM sodium citrate/citric acid, 1.1 M ...Details: Crystallization: hanging drop, 2 uL total, 1:1 protein-to-reservoir. Protein: 11 mg/mL in 50 mM HEPES, 200 mM NaCl, 2 mM DTT, pH 7.5. Reservoir: 100 mM sodium citrate/citric acid, 1.1 M sodium tartrate, pH 5.5. Soaking: 100 mM sodium citrate/citric acid, 1.5 M sodium tartrate, 10% glycerol, 1 mM ligand, pH 5.5. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 22, 2018 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 3.1→117.21 Å / Num. obs: 46257 / % possible obs: 99.7 % / Redundancy: 4.2 % / CC1/2: 0.997 / Rmerge(I) obs: 0.104 / Rpim(I) all: 0.054 / Rrim(I) all: 0.118 / Net I/σ(I): 8.9 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2V1D Resolution: 3.1→117.21 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.947 / SU B: 29.945 / SU ML: 0.219 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.339 / ESU R Free: 0.256 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 201.93 Å2 / Biso mean: 103.707 Å2 / Biso min: 60.66 Å2
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Refinement step | Cycle: final / Resolution: 3.1→117.21 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.1→3.18 Å / Rfactor Rfree error: 0 / 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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