+Open data
-Basic information
Entry | Database: PDB / ID: 3ns9 | ||||||
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Title | Crystal structure of CDK2 in complex with inhibitor BS-194 | ||||||
Components | Cell division protein kinase 2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / protein kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
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 / cyclin-dependent kinase / Cajal body / 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 / response to organic substance / male germ cell nucleus / G1/S transition of mitotic cell cycle / potassium ion transport / DNA Damage/Telomere Stress Induced Senescence / CDK-mediated phosphorylation and removal of Cdc6 / Meiotic recombination / SCF(Skp2)-mediated degradation of p27/p21 / 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 / protein serine kinase activity / DNA repair / 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 / molecular replacement / Resolution: 1.78 Å | ||||||
Authors | Hazel, P. / Freemont, P.S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2010 Title: A Novel Pyrazolo[1,5-a]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human Tumor Xenografts Following Oral Administration. Authors: Heathcote, D.A. / Patel, H. / Kroll, S.H. / Hazel, P. / Periyasamy, M. / Alikian, M. / Kanneganti, S.K. / Jogalekar, A.S. / Scheiper, B. / Barbazanges, M. / Blum, A. / Brackow, J. / Siwicka, ...Authors: Heathcote, D.A. / Patel, H. / Kroll, S.H. / Hazel, P. / Periyasamy, M. / Alikian, M. / Kanneganti, S.K. / Jogalekar, A.S. / Scheiper, B. / Barbazanges, M. / Blum, A. / Brackow, J. / Siwicka, A. / Pace, R.D. / Fuchter, M.J. / Snyder, J.P. / Liotta, D.C. / Freemont, P.S. / Aboagye, E.O. / Coombes, R.C. / Barrett, A.G. / Ali, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3ns9.cif.gz | 78.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3ns9.ent.gz | 56.5 KB | Display | PDB format |
PDBx/mmJSON format | 3ns9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ns/3ns9 ftp://data.pdbj.org/pub/pdb/validation_reports/ns/3ns9 | HTTPS FTP |
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-Related structure data
Related structure data | 1hckS 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: 33976.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDK2 / Plasmid: pProEx / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P24941, cyclin-dependent kinase | ||
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#2: Chemical | #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: 1.99 Å3/Da / Density % sol: 38.18 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 0.1M ammonium acetate, pH 7.8, 6% PEG 3350, VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 26, 2010 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.78→42.431 Å / Num. all: 26364 / Num. obs: 26364 / % possible obs: 99.4 % / Redundancy: 3.3 % / Rsym value: 0.095 / Net I/σ(I): 6.7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1HCK Resolution: 1.78→42.43 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.915 / WRfactor Rfree: 0.2754 / WRfactor Rwork: 0.2101 / Occupancy max: 1 / Occupancy min: 0.8 / FOM work R set: 0.8211 / SU B: 3.451 / SU ML: 0.11 / SU R Cruickshank DPI: 0.1525 / SU Rfree: 0.1538 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.154 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 66.92 Å2 / Biso mean: 29.9882 Å2 / Biso min: 12.09 Å2
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Refinement step | Cycle: LAST / Resolution: 1.78→42.43 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.78→1.828 Å / Total num. of bins used: 20
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