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Yorodumi- PDB-5iex: Crystal structure of (R,S)-S-{4-[(5-Bromo-4-{[(2R,3R)-2-hydroxy-1... -
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-Basic information
Entry | Database: PDB / ID: 5iex | ||||||
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Title | Crystal structure of (R,S)-S-{4-[(5-Bromo-4-{[(2R,3R)-2-hydroxy-1-methylpropyl]oxy}- pyrimidin-2-yl)amino]phenyl}-S-cyclopropylsulfoximide bound to CDK2 | ||||||
Components | Cyclin-dependent kinase 2 | ||||||
Keywords | TRANSFERASE / Antineoplastic Agents / Cyclin-Dependent Kinases / Dose-Response Relationship / Drug / Drug Discovery / HeLa Cells / Molecular Structure / Neoplasms / Protein Kinase Inhibitors / Pyrimidines / Structure-Activity Relationship / Structure-Kinetics Relationship / Sulfoxides / Biophysical Assays / Tumor / Humans | ||||||
Function / homology | Function and homology information cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation ...cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / cyclin-dependent protein kinase activity / Y chromosome / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / X chromosome / PTK6 Regulates Cell Cycle / regulation of anaphase-promoting complex-dependent catabolic process / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / centriole replication / Regulation of APC/C activators between G1/S and early anaphase / centrosome duplication / Telomere Extension By Telomerase / G0 and Early G1 / Activation of the pre-replicative complex / cyclin-dependent protein kinase holoenzyme complex / cellular response to nitric oxide / Cajal body / cyclin-dependent kinase / cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Activation of ATR in response to replication stress / Cyclin E associated events during G1/S transition / Cyclin A/B1/B2 associated events during G2/M transition / Cyclin A:Cdk2-associated events at S phase entry / condensed chromosome / mitotic G1 DNA damage checkpoint signaling / regulation of mitotic cell cycle / regulation of G2/M transition of mitotic cell cycle / cyclin binding / post-translational protein modification / meiotic cell cycle / positive regulation of DNA replication / male germ cell nucleus / response to organic substance / G1/S transition of mitotic cell cycle / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / SCF(Skp2)-mediated degradation of p27/p21 / Meiotic recombination / Orc1 removal from chromatin / Transcriptional regulation of granulopoiesis / Cyclin D associated events in G1 / G2/M transition of mitotic cell cycle / cellular senescence / Regulation of TP53 Degradation / nuclear envelope / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / peptidyl-serine phosphorylation / Ras protein signal transduction / Regulation of TP53 Activity through Phosphorylation / transcription regulator complex / DNA replication / chromosome, telomeric region / endosome / chromatin remodeling / cell division / protein domain specific binding / protein phosphorylation / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA-templated transcription / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / magnesium ion binding / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.03 Å | ||||||
Authors | Ayaz, P. / Andres, D. / Kwiatkowski, D.A. / Kolbe, C. / Lienau, P. / Siemeister, G. / Luecking, U. / Stegmann, C.M. | ||||||
Citation | Journal: Acs Chem.Biol. / Year: 2016 Title: Conformational Adaption May Explain the Slow Dissociation Kinetics of Roniciclib (BAY 1000394), a Type I CDK Inhibitor with Kinetic Selectivity for CDK2 and CDK9. Authors: Ayaz, P. / Andres, D. / Kwiatkowski, D.A. / Kolbe, C.C. / Lienau, P. / Siemeister, G. / Lucking, U. / Stegmann, C.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5iex.cif.gz | 126 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5iex.ent.gz | 102.8 KB | Display | PDB format |
PDBx/mmJSON format | 5iex.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ie/5iex ftp://data.pdbj.org/pub/pdb/validation_reports/ie/5iex | HTTPS FTP |
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-Related 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: 33976.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2, CDKN2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P24941, cyclin-dependent kinase |
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#2: Chemical | ChemComp-6AF / ( |
#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: 2.04 Å3/Da / Density % sol: 39.67 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 10% PEG 3350, 0.2M ammonium acetate, 100mM HEPES pH 7.8 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.918 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.918 Å / Relative weight: 1 |
Reflection | Resolution: 2.03→43.02 Å / Num. obs: 17395 / % possible obs: 97.9 % / Redundancy: 4.34 % / Net I/σ(I): 8.27 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.03→43.02 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.91 / SU B: 13.643 / SU ML: 0.178 / Cross valid method: THROUGHOUT / ESU R: 0.238 / ESU R Free: 0.197 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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 mean: 31.553 Å2
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Refinement step | Cycle: 1 / Resolution: 2.03→43.02 Å
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